Medical hypotheses最新文献

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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.

{"title":"Exploring dual applications of gliptins: A potential host-targeted strategy for diabetes and COVID-19 co-morbidity","authors":"A. Nag , Y.P. Baid , M. Tyagi","doi":"10.1016/j.mehy.2025.111602","DOIUrl":"10.1016/j.mehy.2025.111602","url":null,"abstract":"<div><div>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 <em>in silico</em> 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 <em>in vitro</em> and <em>in vivo</em> 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.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111602"},"PeriodicalIF":2.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437784","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

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}

引用次数: 0

Optic nerve subarachnoid space measurement as the best predictor of post-dural puncture headache after intravertebral anesthesia

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-01 DOI: 10.1016/j.mehy.2024.111557

Xue Zhang , Shuzhen Liu , Xu Yan , Bin Nie , Shiyong Li , Xing Li , Ailin Luo , Yilin zhao

Intravertebral anesthesia is a commonly used method during surgery due to its easy administration, rapid effects, muscle relaxation, and pain control. However, post-dural puncture headache (PDPH) is a frequent complication following intravertebral anesthesia. The primary mechanism of PDPH is the leakage of cerebrospinal fluid (CSF) through the dural puncture site, leading to a decrease in intracranial pressure (ICP). Symptoms typically include a headache that worsens when sitting or standing and improves when lying down, along with possible neck stiffness, nausea, and photophobia. The optic nerve subarachnoid space (ONSS), located behind the globe of the eye within the orbit, is filled with CSF and is continuous with the cranial subarachnoid space. The pressure in this space, often referred to as intraocular pressure (IOP) when discussing eye-related conditions, is typically discussed in the context of its relation to ICP when considering the optic nerve subarachnoid space. Therefore, the measurement of pressure in the ONSS by optic nerve sheath diameter (ONSD) may serve as the best predictor for PDPH, which might be an effective way to reflect changes in intracranial pressure after intravertebral anesthesia, offering valuable information for accurate prediction and prevention of PDPH.

{"title":"Optic nerve subarachnoid space measurement as the best predictor of post-dural puncture headache after intravertebral anesthesia","authors":"Xue Zhang , Shuzhen Liu , Xu Yan , Bin Nie , Shiyong Li , Xing Li , Ailin Luo , Yilin zhao","doi":"10.1016/j.mehy.2024.111557","DOIUrl":"10.1016/j.mehy.2024.111557","url":null,"abstract":"<div><div>Intravertebral anesthesia is a commonly used method during surgery due to its easy administration, rapid effects, muscle relaxation, and pain control. However, post-dural puncture headache (PDPH) is a frequent complication following intravertebral anesthesia. The primary mechanism of PDPH is the leakage of cerebrospinal fluid (CSF) through the dural puncture site, leading to a decrease in intracranial pressure (ICP). Symptoms typically include a headache that worsens when sitting or standing and improves when lying down, along with possible neck stiffness, nausea, and photophobia. The optic nerve subarachnoid space (ONSS), located behind the globe of the eye within the orbit, is filled with CSF and is continuous with the cranial subarachnoid space. The pressure in this space, often referred to as intraocular pressure (IOP) when discussing eye-related conditions, is typically discussed in the context of its relation to ICP when considering the optic nerve subarachnoid space. Therefore, the measurement of pressure in the ONSS by optic nerve sheath diameter (ONSD) may serve as the best predictor for PDPH, which might be an effective way to reflect changes in intracranial pressure after intravertebral anesthesia, offering valuable information for accurate prediction and prevention of PDPH.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111557"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148415","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

Pathological Demand Avoidance is a result of mental process opacity

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-01 DOI: 10.1016/j.mehy.2025.111573

Lana Frankle

引用次数: 0

Bayesian predictive coding hypothesis: Brain as observer’s key role in insight

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-01 DOI: 10.1016/j.mehy.2024.111546

Anirban Dutta

Hypnosis, defined by focused attention and reduced peripheral awareness, integrates psychological processes such as attention, expectancy, and imagery. Self-hypnosis is a process where an individual induces a hypnotic state in themselves to achieve specific goals, such as stress reduction, behaviour modification, or overcoming phobias. This practice involves deep relaxation and heightened focus, allowing suggestions to bypass the conscious mind and influence the subconscious. In contrast, Insight meditation, also known as Vipassana, is a form of mindfulness meditation rooted in Buddhist traditions. Practitioners observe their thoughts, emotions, and bodily sensations as they arise and pass away, gaining deep insights into the nature of reality, impermanence, and the workings of the mind. In this paper, I present a Bayesian Predictive Coding Hypothesis as a theoretical framework to compare Self-hypnosis with Insight meditation that proposes brain processes information by generating and updating predictions about sensory inputs using Bayesian inference where perception is not a passive reception of stimuli, but an active construction based on prior knowledge and expectations. Assuming linear system dynamics and Gaussian noise, I propose that a Kalman filter model functions as an optimal observer subserving Insight meditation, priming the measurement model necessary for effective cognitive control in Self-hypnosis. This Bayesian measurement model is crucial for planning therapeutic cognitive control interventions in functional neurological disorders, which are hypothesized in this paper to be forms of maladaptive learning in adults.

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引用次数: 0

Comment on “Physical exercise and glycemic control: Is HbA1c the best marker for assessing the effects of aerobic training?”

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-02-01 DOI: 10.1016/j.mehy.2024.111560

Thiagarajan Subramanian, Lovedeep Kour

引用次数: 0

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