Medical hypotheses最新文献

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Exploring the role of gut microbiota in the pathogenesis of Kashin-Beck Disease: A Focus on selenium deficiency and T-2 toxin exposure

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-03-10 DOI: 10.1016/j.mehy.2025.111606

Lian Liu , Lulu Bai , Yifan Wu , Yu Zhang , Chaowei Wang , Shujin Li , Yuequan Yuan , Xi Lv , Hui Wang , Yirong Qin , Xiong Guo , Xi Wang , Yujie Ning

Kashin-Beck disease (KBD) is a chronic degenerative osteochondral condition endemic to certain regions, with its etiology and pathogenesis yet to be fully understood. Research indicates that low selenium levels and exposure to T-2 toxin are recognized environmental risk factors associated with KBD. The gut microbiota, a complex assemblage of microorganisms residing in the human gastrointestinal tract, engages in intricate interactions with its metabolites and the host organism, which can have either beneficial or harmful impacts on host health. These interactions may contribute to or influence the development and progression of various diseases. Clinical investigations into osteoarthritis (OA) have demonstrated alterations in the gut microbiota of patients, which are closely associated with the onset of OA. Notably, KBD exhibits clinical and pathological similarities to OA. In light of the relationship between gut microbiota and bone-related diseases, we propose the hypothesis that selenium deficiency and T-2 toxin exposure induce dysbiosis of the gut microbiota, thereby contributing to the pathogenesis of KBD. We hypothesize that the gut microbiota and its metabolites may play a role in the injury or necrosis of chondrocytes induced by inflammatory responses, as well as in the degradation of the chondrocyte extracellular matrix (ECM), via the “cartilage-gut-microbiome” axis. This interaction could result in pathological changes in chondrocytes. Understanding this mechanism may offer novel insights for the treatment and management of KBD.

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引用次数: 0

Sinoatrial node rod cells transplantation into the injured spinal cord as a novel therapeutic approach to improve proper information transmission

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-03-10 DOI: 10.1016/j.mehy.2025.111608

Mohammad Saleh Ranaiy , Dina Rajabi Zadeh , Mozhgan Abasi , Hamed Ghazvini , Misagh Shafizad , Seyedeh Masoumeh Seyedhosseini Tamijani , Raheleh Rafaiee

Spinal cord injury (SCI) is a devastating condition that disrupts neural circuits, leading to severe motor, sensory, and autonomic dysfunction. Despite extensive research, no effective treatment has been established to restore proper information transmission across the injury site. Current therapeutic strategies, including cell therapy and electrical stimulation, have shown promise but remain limited in their ability to fully re-establish functional connectivity. This study proposes a novel therapeutic approach for SCI by implanting sinoatrial node (SAN) rod cells into the injured spinal cord to facilitate electrical signal transmission and restore neural communication. Given their intrinsic ability to conduct electrical impulses in the heart, we hypothesize that SAN rod cells can serve as bioelectrical bridges, reconnecting the severed. We discuss the pathophysiology of SCI, barriers to axonal regeneration, and existing treatment modalities, highlighting the limitations of current interventions. We propose a transplantation strategy involving SAN rod cells and evaluate their potential for integration into the spinal cord. The hypothesis is supported by the role of gap junctions, particularly connexins, in neuronal electrical coupling, which may enable functional interaction between rod cells and spinal neurons. Furthermore, we outline experimental approaches, including in vivo spinal cord transection models and potential methods for generating SAN rod cells from induced pluripotent stem cells. Rod cells, known for their ability to conduct electrical signals without generating action potentials, could theoretically facilitate neural communication across SCI lesions. Their integration into spinal networks via gap junctions may re-establish lost connectivity, potentially improving motor and sensory function.

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引用次数: 0

DPP4 inhibitors and the matters of metaflammation!

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-03-03 DOI: 10.1016/j.mehy.2025.111605

Rohan Magoon

引用次数: 0

“Idiopathic” adhesive capsulitis is caused by reactivation of latent neurotrophic virus involving peripheral nerves around the shoulder capsule: A hypothesis

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-22 DOI: 10.1016/j.mehy.2025.111604

William Zhan Xia , Rosa Ezquerro Cortes , Kuen Foo Chin , Carlos Cobiella , Simon Lambert

The aetiology and pathogenesis of so-called “idiopathic” adhesive capsulitis (IAC), otherwise known as “frozen shoulder” is not well understood. The condition has been compared to the contracture of Dupuytren’s disease, but this appears to be unlikely, and the many modalities of treatment appear to incompletely address the associated symptoms while not affecting the underlying course of the disorder. It is a debilitating and intrusive condition with a characteristic lengthy duration, sharing features with other conditions characterized by initial hyperaemia with subsequent fibrosis. We hypothesize that IAC is caused by reactivation of latent neurotrophic viruses involving peripheral nerves in the shoulder capsule and synovium, predominantly affecting the distribution of branches of the lateral pectoral nerve in which sympathetic efferents from the stellate ganglion pass to the rotator interval of the shoulder. We postulate that IAC is a low-grade infection from reactivation of latent neurotropic herpesvirus or other viruses with similar biological behaviors. This is based on the observations of increased expression of neural markers in shoulder capsule in early IAC, the epidemiological and clinical similarities between IAC and herpes zoster, the recognition of diverse clinical presentations of herpes zoster induced brachial plexopathy, and finally the significant association between herpesvirus infection and idiopathic pulmonary fibrosis and fibrogenic cancers. An improved understanding on the aetiology of IAC may guide future research on identifying the exact pathogen(s), revealing the pathogenesis, facilitate early diagnosis and prognostication of the disease, and more importantly may potentially improve treatment outcomes (and cure the disease) with antiviral therapy or immunomodulation and possibly decrease the incidence of the condition with antiviral vaccine in susceptible subjects.

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引用次数: 0

Exploring dual applications of gliptins: A potential host-targeted strategy for diabetes and COVID-19 co-morbidity

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-17 DOI: 10.1016/j.mehy.2025.111602

A. Nag , Y.P. Baid , M. Tyagi

The COVID-19 pandemic has underscored the urgent need for innovative therapeutic strategies, particularly for vulnerable populations such as individuals with Type 2 diabetes mellitus (T2DM), who face heightened risks of severe complications. Gliptins, widely used as dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM management, have emerged as promising candidates for therapeutic repurposing against SARS-CoV-2 infection. This study hypothesizes that gliptins can serve as dual-purpose therapeutic agents, targeting both T2DM and SARS-CoV-2, by leveraging their inhibitory effects on host receptors such as DPP4 and ACE2, which are implicated in viral entry and pathogenesis. There is also an established association between the increased COVID-19 risk with the hyperglycemia through SLC5A receptor variants. Preliminary evidence from in silico analyses supports this hypothesis, demonstrating strong binding affinities of gliptins, particularly linagliptin and alogliptin, to key receptors involved in SARS-CoV-2 infection. This dual targeting potential suggests that gliptins could hypothetically reduce viral replication while simultaneously managing hyperglycemia. To further validate this hypothesis, molecular dynamics simulations, followed by in vitro and in vivo studies, are proposed. The ultimate goal is to evaluate the clinical utility of gliptins, either as standalone treatments or in combination with other therapies, in managing COVID-19 among diabetic patients. This proposed therapeutic strategy not only addresses the immediate challenges of treating COVID-19 in patients with comorbid T2DM but also offers a robust host-targeted approach that is resilient to viral mutations. If successful, it could redefine the management of comorbid conditions in infectious disease scenarios, offering a sustainable and broadly applicable solution to future public health crises.

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引用次数: 0

Circadian rhythm as a key target for endogenous testosterone restoration in aging men

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-12 DOI: 10.1016/j.mehy.2025.111594

Kuo-Jen Lin , Hong-Kai Wang , Yu-Hsiang Lin

引用次数: 0

Correspondence to ’A quantum mechanical explanation for auditory-visual hallucinations by Liam Greenacre’

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-11 DOI: 10.1016/j.mehy.2025.111593

Víctor Manuel Asensio-Sánchez

引用次数: 0

Using the V127 prion variant for prion disease gene therapy: A hypothesis

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-02 DOI: 10.1016/j.mehy.2025.111584

Michael Bordonaro

Prion diseases are fatal neurodegenerative disorders caused by abnormal folding of prion proteins. Prion diseases can be sporadic, genetic, or acquired. In Papua New Guinea, the Fore people were afflicted by an acquired prion disease, kuru, caused by the consumption of prion-infected brain tissue. Owing to the strong selective pressure of this community-wide disease, many Fore people are heterozygous for the G127V prion variant that confers kuru resistance. Animal models demonstrated that mice heterozygous for the variant prion are resistant to both kuru and classical CJD but can still be infected with variant CJD. However, mice homozygous for the V127 variant form are resistant to all forms of prion infection, and further data demonstrate that this variant suppresses prion disease in a dose-dependent manner. Advances have been made in gene therapy for the central nervous system. The hypothesis proposed is that exogenous overexpression of the V127 prion variant in the brains of prion disease patients and potential patients interferes with the propagation of misfolded prion protein molecules, thereby arresting disease progression and possibly preventing initiation. Therefore, this V127 approach could be therapeutic for prion disease and preventive for individuals with genetic prion disease mutations. Hence, this paper proposes gene therapy for prion disease via the overexpression of the V127 variant in patient brain cells. The objectives of this approach would be to delay and/or reduce disease progression, to possibly be curative for sporadic and acquired prion disease, and as a preventive measure against genetic prion disease.

{"title":"Using the V127 prion variant for prion disease gene therapy: A hypothesis","authors":"Michael Bordonaro","doi":"10.1016/j.mehy.2025.111584","DOIUrl":"10.1016/j.mehy.2025.111584","url":null,"abstract":"<div><div>Prion diseases are fatal neurodegenerative disorders caused by abnormal folding of prion proteins. Prion diseases can be sporadic, genetic, or acquired. In Papua New Guinea, the Fore people were afflicted by an acquired prion disease, kuru, caused by the consumption of prion-infected brain tissue. Owing to the strong selective pressure of this community-wide disease, many Fore people are heterozygous for the G127V prion variant that confers kuru resistance. Animal models demonstrated that mice heterozygous for the variant prion are resistant to both kuru and classical CJD but can still be infected with variant CJD. However, mice homozygous for the V127 variant form are resistant to all forms of prion infection, and further data demonstrate that this variant suppresses prion disease in a dose-dependent manner. Advances have been made in gene therapy for the central nervous system. The hypothesis proposed is that exogenous overexpression of the V127 prion variant in the brains of prion disease patients and potential patients interferes with the propagation of misfolded prion protein molecules, thereby arresting disease progression and possibly preventing initiation. Therefore, this V127 approach could be therapeutic for prion disease and preventive for individuals with genetic prion disease mutations. Hence, this paper proposes gene therapy for prion disease via the overexpression of the V127 variant in patient brain cells. The objectives of this approach would be to delay and/or reduce disease progression, to possibly be curative for sporadic and acquired prion disease, and as a preventive measure against genetic prion disease.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"196 ","pages":"Article 111584"},"PeriodicalIF":2.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143158692","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}

引用次数: 0

Can WGX-50 be a potential therapy to treat tumor by inhibiting mitochondrial reactive oxidative species?

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-02 DOI: 10.1016/j.mehy.2025.111583

Adil Farooq, Guihua Jia, Muhammad Rizwan, Muhammad Imran, Dongqing Wei

Mitochondria are crucial for cellular metabolism, producing adenosine triphosphate and reactive oxygen species. While often viewed as harmful by-products, reactive oxygen species are important for cell signalling, gene expression, and stress adaptation. Abnormal production is linked to conditions like, cancer, where it promotes tumor growth and treatment resistance. Recent studies focus on novel drug WGX-50 extracted from Zanthoxylum Bungeanum Maxim, which targets mitochondrial reactive oxidative species, causing mt-DNA damage and triggering downstream effects. Elevated oxidative species also induce lipid oxidative stress, leading to ferroptosis, a regulated form cell death. WGX-50 can suppress inflammatory cytokines and VEGF, inhibiting angiogenesis and creating less favorable tumor microenvironment, impeding growth. Additionally, WGX-50 could alter the PD-L1/EV pathway, potentially reversing immune suppression and shifting toward an anti-tumor immune response, which enhancing immunotherapy effectiveness. This hypothesis can be tested using in-vitro and in-vivo models, comparing the control group with WGX-50 treatment in different doses intervals after tumor induction. WGX-50 will be the mt-ROS inhibitor is crucial in tumor progression, OS and inflammation. By inhibiting mt-ROS it could be a breakthrough in cancer treatment.

{"title":"Can WGX-50 be a potential therapy to treat tumor by inhibiting mitochondrial reactive oxidative species?","authors":"Adil Farooq, Guihua Jia, Muhammad Rizwan, Muhammad Imran, Dongqing Wei","doi":"10.1016/j.mehy.2025.111583","DOIUrl":"10.1016/j.mehy.2025.111583","url":null,"abstract":"<div><div>Mitochondria are crucial for cellular metabolism, producing adenosine triphosphate and reactive oxygen species. While often viewed as harmful by-products, reactive oxygen species are important for cell signalling, gene expression, and stress adaptation. Abnormal production is linked to conditions like, cancer, where it promotes tumor growth and treatment resistance. Recent studies focus on novel drug WGX-50 extracted from Zanthoxylum Bungeanum Maxim, which targets mitochondrial reactive oxidative species, causing mt-DNA damage and triggering downstream effects. Elevated oxidative species also induce lipid oxidative stress, leading to ferroptosis, a regulated form cell death. WGX-50 can suppress inflammatory cytokines and VEGF, inhibiting angiogenesis and creating less favorable tumor microenvironment, impeding growth. Additionally, WGX-50 could alter the PD-L1/EV pathway, potentially reversing immune suppression and shifting toward an anti-tumor immune response, which enhancing immunotherapy effectiveness. This hypothesis can be tested using in-vitro and in-vivo models, comparing the control group with WGX-50 treatment in different doses intervals after tumor induction. WGX-50 will be the mt-ROS inhibitor is crucial in tumor progression, OS and inflammation. By inhibiting mt-ROS it could be a breakthrough in cancer treatment.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"196 ","pages":"Article 111583"},"PeriodicalIF":2.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143158747","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}

引用次数: 0

Engineered probiotics that produce antibiotic binding sites: A potential strategy to protect gut microbiome and prevent antibiotic resistance

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-01 DOI: 10.1016/j.mehy.2024.111558

Mobina Saleh , Ruhollah Heydari , Mohammad Reza Ghanbari Boroujeni , Ramin Abiri

Antibiotics play a pivotal role in combating infectious diseases globally, but their widespread use damages the gut microbiome, resulting in various diseases and the emergence and spread of antibiotic-resistant bacteria. Reducing gut exposure to antibiotics during treatments is crucial for maintaining gut homeostasis. We suggest using edible engineered probiotics that express genes encoding antibiotic-binding peptides as a novel method to neutralize antibiotics and protect the gut flora. To produce these genetically modified organisms, CRISPR-Cas or other genome editing methods can be utilized. By inserting the gene encoding antibiotic-binding peptides along with the secretion complex into the probiotic, these engineered probiotics produce and secrete these peptides. The peptides that mimic natural antibiotic-binding sites specifically bind to and neutralize the intestinal drug residues (the administered antibiotics for infections outside the gut) and preserve the gut microbiome. Since the probiotics colonize and secrete these peptides in the distal intestine, antibiotic absorption in the proximal intestine remains unaffected. Using these engineered probiotics may reduce the emergence of antibiotic-resistant bacteria and prevent pathogen colonization. Further research in this area could advance the development of this promising approach.

{"title":"Engineered probiotics that produce antibiotic binding sites: A potential strategy to protect gut microbiome and prevent antibiotic resistance","authors":"Mobina Saleh , Ruhollah Heydari , Mohammad Reza Ghanbari Boroujeni , Ramin Abiri","doi":"10.1016/j.mehy.2024.111558","DOIUrl":"10.1016/j.mehy.2024.111558","url":null,"abstract":"<div><div>Antibiotics play a pivotal role in combating infectious diseases globally, but their widespread use damages the gut microbiome, resulting in various diseases and the emergence and spread of antibiotic-resistant bacteria. Reducing gut exposure to antibiotics during treatments is crucial for maintaining gut homeostasis. We suggest using edible engineered probiotics that express genes encoding antibiotic-binding peptides as a novel method to neutralize antibiotics and protect the gut flora. To produce these genetically modified organisms, CRISPR-Cas or other genome editing methods can be utilized. By inserting the gene encoding antibiotic-binding peptides along with the secretion complex into the probiotic, these engineered probiotics produce and secrete these peptides. The peptides that mimic natural antibiotic-binding sites specifically bind to and neutralize the intestinal drug residues (the administered antibiotics for infections outside the gut) and preserve the gut microbiome. Since the probiotics colonize and secrete these peptides in the distal intestine, antibiotic absorption in the proximal intestine remains unaffected. Using these engineered probiotics may reduce the emergence of antibiotic-resistant bacteria and prevent pathogen colonization. Further research in this area could advance the development of this promising approach.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111558"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148432","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}

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Medical hypotheses

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