Medical hypotheses最新文献

{"title":"Can WGX-50 be a potential therapy to treat tumor by inhibiting mitochondrial reactive oxidative species?","authors":"Adil Farooq,&nbsp;Guihua Jia,&nbsp;Muhammad Rizwan,&nbsp;Muhammad Imran,&nbsp;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}

{"title":"Engineered probiotics that produce antibiotic binding sites: A potential strategy to protect gut microbiome and prevent antibiotic resistance","authors":"Mobina Saleh ,&nbsp;Ruhollah Heydari ,&nbsp;Mohammad Reza Ghanbari Boroujeni ,&nbsp;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}

{"title":"Optic nerve subarachnoid space measurement as the best predictor of post-dural puncture headache after intravertebral anesthesia","authors":"Xue Zhang ,&nbsp;Shuzhen Liu ,&nbsp;Xu Yan ,&nbsp;Bin Nie ,&nbsp;Shiyong Li ,&nbsp;Xing Li ,&nbsp;Ailin Luo ,&nbsp;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}

{"title":"Pathological Demand Avoidance is a result of mental process opacity","authors":"Lana Frankle","doi":"10.1016/j.mehy.2025.111573","DOIUrl":"10.1016/j.mehy.2025.111573","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111573"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148431","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":"Bayesian predictive coding hypothesis: Brain as observer’s key role in insight","authors":"Anirban Dutta","doi":"10.1016/j.mehy.2024.111546","DOIUrl":"10.1016/j.mehy.2024.111546","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111546"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148396","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":"Comment on “Physical exercise and glycemic control: Is HbA1c the best marker for assessing the effects of aerobic training?”","authors":"Thiagarajan Subramanian,&nbsp;Lovedeep Kour","doi":"10.1016/j.mehy.2024.111560","DOIUrl":"10.1016/j.mehy.2024.111560","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111560"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148416","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":"Interpretation of subjective ratings within pain research: What about context effects? an induced secondary hyperalgesia example","authors":"Niels Jansen,&nbsp;Marie-Laure A.H.C. Snijders,&nbsp;Jan R. Buitenweg","doi":"10.1016/j.mehy.2025.111571","DOIUrl":"10.1016/j.mehy.2025.111571","url":null,"abstract":"<div><div>In many experimental and clinical studies, subjective ratings of experimentally induced pain experiences are used to evaluate the nociceptive function. However, our understanding of how these subjective ratings are produced and influenced is limited. Not taking into account variability in how the subjective responses are produced, e.g. due to experience with (experimental) pain, might lead to biased, underpowered or even misinterpreted studies or clinical decisions. Here, we illustrate such variability in the case of studying secondary hyperalgesia using High Frequency Stimulation (HFS) as a conditioning stimulus. Recently, different findings have been reported related to the effect of HFS on single electrical stimuli. While most studies report an increased pain rating at the test electrode after HFS relative to the control site, in some studies this difference between test and control ratings is the result of a decrease in pain ratings at the control site. In these reports, the observations are explained by nociceptive mechanisms like habituation or descending inhibition. In our view these mechanisms do not (fully) explain the observable event, nor the differences between the studies. Here, we provide a phenomenological analysis of the observable event and based on this analysis hypothesize that ratings can be affected by prior experience with experimental stimuli (i.e. familiarization with HFS). Acceptance of the hypothesis suggests the (co–)existence of alternative mechanisms at experiments with HFS, as earlier suggested underlying mechanisms are unable to explain these observations. We argue that both the observable event and the differences between the studies can be explained by mechanisms underlying so-called context effects, i.e. well-known phenomena in other sensory modalities whereby the participant’s response is altered based on earlier provided stimuli. Importantly, from a theoretical perspective context effects could (have) play(ed) a role in (many) more experimental procedures within pain research than only when HFS is used, but seemingly to date have not received attention. Consequently, with some experimental procedures within pain research, observed variation might be wrongly attributed to changes in nociceptive function due to an explanatory focus on nociceptive mechanisms. On the short-term, acceptance of the hypothesis highlights an urgent need to perform research in which the effect and magnitude of context effects are evaluated in commonly performed procedures within pain research. On the long-term, dependent on the findings of these studies, this might lead to revisiting not only experimental (familiarization) procedures, but also revising the way earlier results from these experimental procedures have been interpreted.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111571"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148433","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":"A quantum mechanical explanation for auditory-visual hallucinations","authors":"Liam Greenacre","doi":"10.1016/j.mehy.2024.111554","DOIUrl":"10.1016/j.mehy.2024.111554","url":null,"abstract":"<div><div>Auditory-visual hallucinations might be caused by Quantum Mechanics. The Many-Worlds Interpretation suggests those who have hallucinations might be experiencing alternate realities due to the unique nature of the quantum. Hallucinations, in part to their quantum nature, are neither biological or social-environmental. On the other hand, the scholarship on the origin of Auditory-Visual Hallucinations usually focuses on either the biological or the social-environmental. There is a range of evidence to suggest that quantum mechanics operates in the brain, like EEGs and the nature of mental states, but the social dynamic is introduced via the Many-Worlds Interpretation. The hypothesis that hallucinations are the result of the Many-Worlds Interpretation is reached through a consideration of quantum biology, optics and acoustics. The proposed hypothesis allows us to consider potential therapeutic and medical benefits of the theory, potentially improving the lives of patients via potential technologies or through reducing the trivialisation of their experiences.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111554"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148413","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":"Exercise-induced intraventricular pressure gradient may be the cause of sudden cardiac death in patients with unknown cardiac disease","authors":"Nuno Cotrim ,&nbsp;Hugo Café ,&nbsp;Pedro Cordeiro ,&nbsp;Jorge Guardado ,&nbsp;Luís Baquero ,&nbsp;Carlos Cotrim","doi":"10.1016/j.mehy.2024.111552","DOIUrl":"10.1016/j.mehy.2024.111552","url":null,"abstract":"<div><div>Sudden cardiac death (SCD) is a tragedy at any age and under any circumstances, but it is especially poignant, and fortunately very rare, when it takes the life of an athlete, a person who represents health and a healthy lifestyle. Sports cardiologists worldwide have worked to quantify the incidence of SCD in athletes, identify risk factors, develop pre-participation screening tools, and formulate plans to address on-field SCD. While progress has been made, there is still much to do to make both competitive and recreational sports safer for individuals with known cardiac disease and athletes without known or suspected cardiac abnormalities.</div><div>We recently published the case of an athlete who practices triathlon and underwent medical evaluation after an episode of aborted sudden death. The complete diagnostic workup including a complete genetic study for myocardiopathy had normal results. An exercise stress echocardiogram (ESE) was finally performed during which he developed a significant intraventricular pressure gradient (IVPG) − a possible cause of ischemia − over 100 mmHg with an end-systolic peak at the end of exercise that was associated with frequent premature ventricular complexes.</div><div>We hypothesize the possible role of ESE for IVPG assessment in athletes who have unexplained symptoms related to exercise or aborted sudden death. In our opinion, it should be considered useful and used by routine to improve the clinical approach of this group of patients, detecting possible high-risk athletes.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111552"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148409","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":"Activation of resident immune cells induces enteric neuronal death","authors":"João Janilson da Silva Sousa ,&nbsp;Vanessa de Sousa do Vale ,&nbsp;Rafael da Silva Prudêncio ,&nbsp;Diva de Aguiar Magalhães ,&nbsp;Viviane Pinheiro Alves de Almeida ,&nbsp;Antônio Kleiton de Sousa ,&nbsp;Tino Marcos Lino da Silva ,&nbsp;Kaique Aguiar Souza ,&nbsp;Vanderlene Oliveira Rodrigues ,&nbsp;André Luiz dos Reis Barbosa","doi":"10.1016/j.mehy.2024.111555","DOIUrl":"10.1016/j.mehy.2024.111555","url":null,"abstract":"<div><div>Resident immune cells are involved in the pathogenesis of inflammatory bowel diseases (IBDs). Studies have already demonstrated that these cells, mainly mast cells and macrophages, are close to and in communication with neurons of the enteric nervous system (ENS). Enteric neurons organized in ganglions participate in processes such as control of motility, secretory functions, absorption and blood flow. Morphological and functional changes in these neurons can cause intestinal damage, such as changes in intestinal motility and diarrhea, common features of IBD. Uncontrolled or unregulated activation of mast cells can also interfere with intestinal homeostasis and generate tissue dysfunction and promote inflammation in various gastrointestinal diseases. These cells can also act by releasing mediators that activate enteric glial cells (EGC), leading to reactive gliosis. Despite being recognized as essential regulators of neuronal function in the ENS, when activated by injuries and inflammatory processes, these cells can proliferate and undergo broad activation that, in association with other cells of the external muscular layer of the intestine (neutrophils, monocytes, resident macrophages and smooth muscles) produces and releases pro-inflammatory mediators. This pro-inflammatory action also involves the participation of the beta fraction of the calcium-binding protein S100 (S100β), which despite being found in other cells, in the intestine its expression is limited to EGC. The increase in the expression of this protein may be responsible for the death of neurons, through the activation of receptors for advanced glycation end products (RAGE) and consequent activation of the nuclear transcription factor-κB (NFκB). RAGE-type receptors are expressed in several cells, including their presence in macrophages. It is known that interactions between macrophages and the ENS interfere with intestinal motility, serve as a protective mechanism during injuries and infections, but can also contribute to tissue damage and other gastrointestinal disorders. Therefore, our hypothesis suggests that mast cells and macrophages, resident immune cells, are involved in enteric neuronal death, through the activation of EGCs and the release of pro-inflammatory factors.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111555"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148417","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}