Medical hypotheses最新文献

英文中文

Stress-conditioned small extracellular vesicles from young cells to restore resilience in aging 来自年轻细胞的应力条件下的小细胞外囊泡，以恢复衰老的弹性

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-16 DOI: 10.1016/j.mehy.2026.111886

Julio Buñay, Philippe de Medina, Marc Poirot, Sandrine Silvente-Poirot

Aging is characterized by a progressive decline in cellular stress responses, including oxidative stress resistance, mitochondrial quality control, DNA repair, and autophagy. Small extracellular vesicles (sEVs) released by all cell types are now recognized as key mediators of intercellular communication, particularly under stress conditions. sEVs derived from cells exposed to controlled, non-lethal stressors (e.g., hypoxia, oxidative, mitochondrial, or genotoxic stress) can carry protective molecules that promote stress adaptation and repair in recipient cells. We propose that stress-conditioned sEVs from young cells can restore adaptive stress responses and repair capacity in aging tissues by delivering molecular mediators that are diminished or dysregulated in aged cells. This concept builds on three well-established principles: (1) the content of sEVs reflects the physiological or stress state of the donor cell; (2) sEVs released from stressed cells convey adaptive mediators that promote resilience and repair in recipient cells; and (3) both stress-adaptive responses and intercellular communication are altered in the elderly. This hypothesis proposes that sEVs released by stress-conditioned young cells could constitute a novel gerotherapeutic approach capable of restoring adaptive stress responses and exerting beneficial effects on multiple hallmarks of aging in aged organisms. We discuss the biological rationale, supporting evidence, and experimental models to test this concept.

衰老的特征是细胞应激反应的逐渐下降，包括氧化应激抵抗、线粒体质量控制、DNA修复和自噬。所有细胞类型释放的小细胞外囊泡（sev）现在被认为是细胞间通讯的关键介质，特别是在应激条件下。sev来源于暴露于受控、非致死应激源（如缺氧、氧化、线粒体或基因毒性应激）的细胞，可携带促进受体细胞适应应激和修复的保护性分子。我们提出，来自年轻细胞的应激条件sev可以通过传递在衰老细胞中减少或失调的分子介质来恢复衰老组织的适应性应激反应和修复能力。这一概念建立在三个公认的原则之上：(1)sev的含量反映了供体细胞的生理或应激状态；(2)应激细胞释放的sev传递适应性介质，促进受体细胞的恢复和修复；(3)老年人的应激适应反应和细胞间通讯都发生了改变。这一假设表明，应激条件下的年轻细胞释放的sev可能构成一种新的老年治疗方法，能够恢复适应性应激反应，并对衰老生物体的多种衰老特征产生有益影响。我们讨论了生物学原理、支持证据和实验模型来测试这一概念。

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引用次数: 0

Active Inference as a theoretical framework for external locus of control in chronic pain: the role of aberrant interoceptive integration 主动推理作为慢性疼痛外部控制点的理论框架：异常内感受整合的作用

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-12 DOI: 10.1016/j.mehy.2026.111878

Yuri Cordeiro Szeremeta

Perceived control is a transdiagnostic feature across chronic pain. The Locus of Control is a patient’s personality trait that refers to a belief about the extent to which they have control over their health outcomes. From a phenomenological point of view, the prevalence of internal or external dimensions of Locus of Control indicates how individuals operate certain cognitive systems and how they perceive different forces that influence their lives. Consequently, it is a key indicator of whether treatment will be successful or unsuccessful. However, the neural pathways and belief systems that underlie this personality trait remain poorly understood. This article raises the hypothesis that the theoretical basis of Active Inference may explain a propensity for external Locus of Control in chronic pain sufferers.

感知控制是慢性疼痛的一种跨诊断特征。控制点是患者的人格特征，指的是他们对自己健康结果的控制程度的信念。从现象学的角度来看，控制点的内部或外部维度的流行表明了个体如何操作某些认知系统，以及他们如何感知影响他们生活的不同力量。因此，它是治疗成功与否的关键指标。然而，这种人格特质背后的神经通路和信念系统仍然知之甚少。本文提出主动推理的理论基础可以解释慢性疼痛患者的外部控制点倾向。

引用次数: 0

Vestibular migraine, food triggers, and motion sickness: Revisiting an evolutionary hypothesis 前庭偏头痛、食物诱因和晕动病：重新审视一个进化假说

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-10 DOI: 10.1016/j.mehy.2026.111875

Ariel A. Winnick , Tzu-Pu Chang

Patients with vestibular migraine (VM) are often prone to motion sickness, though the reason for this remains unclear. At the same time, migraine, and specifically VM, can be triggered by certain foods, but the underlying pathophysiology for this is also unknown. An earlier “toxin hypothesis” of motion sickness suggested that through evolution, the vestibular system developed as an alarm mechanism to detect ingested toxins, triggering the symptoms of motion sickness. Building on this idea, we revisit and extend it to an evolutionary hypothesis specifically linking VM and motion sickness. We propose that VM in migraineurs represents an overly sensitive alarm system capable of detecting even subtle neurotoxins in spoiled or degraded foods, substances commonly identified in modern society as migraine-triggers. This evolutionary hypothesis of VM provides a logical and contextual explanation for the observed links between VM, migraine-triggering foods, and motion sickness.

患有前庭偏头痛（VM）的患者通常容易出现晕动病，尽管其原因尚不清楚。与此同时，偏头痛，特别是VM，可以由某些食物引发，但其潜在的病理生理学也未知。早前关于晕动病的“毒素假说”认为，通过进化，前庭系统发展成为一种警报机制，可以检测摄入的毒素，从而引发晕动病的症状。在此基础上，我们重新审视并将其扩展到一个进化假设，特别是将虚拟机和晕动病联系起来。我们认为偏头痛患者的VM代表了一个过于敏感的警报系统，能够检测到变质或降解食物中甚至微妙的神经毒素，这些物质在现代社会中通常被认为是偏头痛的诱因。这种VM的进化假说为VM、引发偏头痛的食物和晕动病之间观察到的联系提供了一种合乎逻辑的上下文解释。

引用次数: 0

Virtual reality-paired opioid analgesia as contextual prophylaxis against iatrogenic opioid addiction: a hypothesis 虚拟现实配对阿片类镇痛作为预防医源性阿片类药物成瘾的情境：一个假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-08 DOI: 10.1016/j.mehy.2026.111874

Austin A. Barr

Opioid analgesics are indispensable for treating moderate-severe inpatient pain, yet even supervised use can precipitate long-term opioid use or opioid use disorder (OUD) in a small but consequential fraction of patients. Current prevention approaches emphasize screening, dosing, and duration, but rarely treat context as a modifiable risk factor. Pavlovian models show that drug effects become tightly linked to environmental cues, influencing tolerance, craving, and overdose risk; conversely, major contextual changes can disrupt addictive patterns. Virtual reality (VR) offers immersive, controllable contexts that already demonstrate analgesic and anxiolytic benefits, and can reliably engage drug-related cue learning. The present paper hypothesizes that systematically pairing inpatient opioid administration with distinctive, varied VR contexts could ‘capture’ opioid-associated learning within artificial contexts and reduce generalization of conditioned responses to post-discharge environments. Combined with VR’s intrinsic analgesic effects, which may reduce total opioid exposure, this strategy could act as a multi-level behavioral prophylaxis against persistent opioid use post-discharge. The conditioning rationale, potential risks, implementation principles, and a three-arm trial to test VR-based contextual prophylaxis during medical opioid therapy are discussed.

阿片类镇痛药对于治疗中重度住院患者疼痛是必不可少的，但即使在监督下使用，也会导致一小部分患者长期使用阿片类药物或阿片类药物使用障碍（OUD）。目前的预防方法强调筛查、剂量和持续时间，但很少将环境视为可改变的风险因素。巴甫洛夫模型表明，药物效应与环境因素密切相关，影响耐受性、渴望和过量风险；相反，重大的环境变化会破坏成瘾模式。虚拟现实（VR）提供了身临其境的可控环境，已经证明了镇痛和抗焦虑的好处，并且可以可靠地参与与药物相关的线索学习。本文假设，系统地将住院患者的阿片类药物管理与独特的、不同的VR环境相结合，可以在人工环境中“捕获”阿片类药物相关的学习，并减少对出院后环境的条件反应的泛化。结合VR的内在镇痛作用，可以减少阿片类药物的总暴露，该策略可以作为一种多层次的行为预防，防止出院后持续使用阿片类药物。本文讨论了在阿片类药物治疗期间测试基于vr的情境预防的条件作用原理、潜在风险、实施原则和三组试验。

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引用次数: 0

A hypothesis on cochlear architecture: Non-intersecting spiral geometry as a determinant of auditory function 一个关于耳蜗结构的假设：不相交的螺旋几何是听觉功能的决定因素

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-02 DOI: 10.1016/j.mehy.2026.111872

Lela Migirov

The human cochlea, the organ of hearing, is a conical spiral structure composed of the scala vestibuli, scala tympani, and scala media. Its spiral geometry is thought to arise from spatial constraints within the temporal bone and from the redistribution of wave energy, thereby enhancing sensitivity to lower-frequency, speech-related sounds. The cochlea is fully formed at birth, and congenital hearing loss is frequently associated with structural abnormalities of this organ. In this work, cochlear anatomy is described as a system of three non-intersecting spiral chambers that constitute a core architectural constraint governing sound propagation and encoding. It is hypothesized that the integrity of this non-intersecting spiral architecture is essential for normal auditory function, and that disruption of this organization contributes to congenital hearing impairment. Conceptual parallels between cochlear geometry, Fermat’s spiral, and spiral motifs in prehistoric art are presented as illustrative correspondences rather than causal relationships, based on their shared non-intersecting spiral pattern.

人的耳蜗是听觉器官，是由前庭耳蜗、中耳蜗和中耳蜗组成的圆锥形螺旋结构。它的螺旋形状被认为是由于颞骨内的空间限制和波能量的重新分配，从而增强了对低频语音相关声音的敏感性。耳蜗在出生时完全形成，先天性听力损失通常与该器官的结构异常有关。在这项工作中，耳蜗解剖被描述为一个由三个不相交的螺旋腔组成的系统，它们构成了控制声音传播和编码的核心结构约束。据推测，这种不相交的螺旋结构的完整性对正常听觉功能至关重要，而这种组织的破坏会导致先天性听力障碍。耳蜗几何、费马螺旋和史前艺术中的螺旋图案之间的概念上的相似之处是基于它们共享的不相交的螺旋图案，作为说明性的对应关系而不是因果关系。

引用次数: 0

Targeting conserved dynamic regions of SARS-CoV-2 spike protein identified by normal mode analysis for broad-spectrum antiviral therapy 利用正常模式分析确定的SARS-CoV-2刺突蛋白的保守动态区域进行广谱抗病毒治疗

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2026-01-02 DOI: 10.1016/j.mehy.2026.111873

Junhong Lü

The continuous emergence of SARS-CoV-2 variants challenges conventional antiviral strategies that targets highly mutable epitopes or enzymatic active sites. We propose a novel hypothesis centered on targeting the conserved dynamic regions of the SARS-CoV-2 spike (S) glycoprotein, which govern its large-scale conformational transitions. Through normal mode analysis (NMA), these regions have been identified as critical dynamic hotspots that facilitate an allosteric transition from the closed to the open, ACE2-accessible state. We hypothesize that small molecules or peptides designed to bind these hotspots could act as conformational locks, thereby providing broad-spectrum antiviral activity. The feasibility of targeting the physical dynamics of the spike protein is supported by independent studies on its mechanical vulnerability. While identifying druggable allosteric pockets and achieving experimental validation still need be overcome before practical realization, this strategy represents a paradigm shift from static, structure-based targeting to dynamic allostery. It offers a potentially variant-resilient therapeutic approach against both current and future threats from coronaviruses.

SARS-CoV-2变体的不断出现挑战了针对高度可变的表位或酶活性位点的传统抗病毒策略。我们提出了一个新的假设，主要针对SARS-CoV-2尖峰(S)糖蛋白的保守动态区域，这些区域控制着其大规模的构象转变。通过正态分析（NMA），这些区域被确定为关键的动态热点，促进从封闭到开放，ace2可访问状态的变构转变。我们假设设计用于结合这些热点的小分子或肽可以作为构象锁，从而提供广谱抗病毒活性。针对刺突蛋白物理动力学的可行性得到了对其机械脆弱性的独立研究的支持。虽然在实际实现之前，确定可药物化的变构口袋和实现实验验证仍然需要克服，但该策略代表了从静态，基于结构的靶向到动态变构的范式转变。它为应对当前和未来冠状病毒的威胁提供了一种潜在的抗变异治疗方法。

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引用次数: 0

Is pain perception of a change in information? 痛觉是一种信息的变化吗？

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-30 DOI: 10.1016/j.mehy.2025.111870

Paula A. Tello Prieto, David A. Miranda

We hypothesize that pain is the perception of a change in information by the organism that experiences it. This view departs from traditional biological, psychological, and social frameworks by framing pain not as a direct response to tissue injury or emotional distress, but as the detection of significant informational disturbance within the nervous system. We suggest that the nociceptive, pathological, and psychological forms of pain can be understood as variations in information flow rather than as distinct biological mechanisms. Information theory, particularly measures based on entropy, may offer a quantitative way to test this hypothesis by linking changes in neural information processing to subjective perception of pain. By proposing pain as an informational phenomenon, this hypothesis opens new perspectives for its diagnosis, management, and integration into a unified theoretical framework.

我们假设疼痛是机体对信息变化的感知。这种观点背离了传统的生物学、心理学和社会框架，认为疼痛不是对组织损伤或情绪困扰的直接反应，而是对神经系统中重大信息干扰的检测。我们认为，痛觉、病理和心理形式的疼痛可以理解为信息流的变化，而不是不同的生物机制。信息论，特别是基于熵的测量方法，可以通过将神经信息处理的变化与疼痛的主观感知联系起来，提供一种定量的方法来检验这一假设。通过提出疼痛是一种信息现象，这一假说为其诊断、管理和整合到一个统一的理论框架中开辟了新的视角。

引用次数: 0

Bio-integrated ultrasound emission hypothesis in engineered amoeboid cells 工程变形虫细胞的生物集成超声发射假说

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-29 DOI: 10.1016/j.mehy.2025.111871

Min Tae Kim

We propose a theoretical framework for engineering amoeboid cells as mobile bio-integrated ultrasonic emitters. The cells migrate within the interstitial space rather than within capillary lumens, where spatial constraints (5–8

μ

m diameter) would otherwise prohibit transit. Amoebae in the 15–25

μ

m size range can exploit their native locomotion mechanisms for environmental exploration, while transiently adopting an anchored state in which cytoskeletal tension stabilizes membrane resonance for efficient ultrasonic emission in the 0.5–2 MHz range. Acoustic radiation in this regime scales strongly with cell radius, enabling detectable remote signaling without requiring vascular circulation. The platform integrates genetically encoded piezoelectric or electromotile proteins (e.g., prestin variants), cytoskeletal tension tuning, and magnetoelastic nanoparticle resonators based on superparamagnetic iron oxide nanoparticles (SPIONs) to achieve controlled, directional ultrasound pulses under an external magnetic field. This dual-mode architecture — mobile sensing and anchored communication — supports distributed biological navigation, intercellular messaging, and potential therapeutic actuation. The framework establishes feasibility conditions and design parameters for future experimental realization.

我们提出了一个理论框架工程阿米巴细胞作为移动的生物集成超声发射器。细胞在间隙内迁移，而不是在毛细血管腔内，否则空间限制（5-8 μm直径）会禁止迁移。在15-25 μm尺寸范围内的变形虫可以利用其固有的运动机制进行环境探测，而在0.5-2 MHz范围内，变形虫暂时采用锚定状态，细胞骨架张力稳定膜共振，从而实现高效的超声发射。在这种情况下，声辐射与细胞半径密切相关，无需血管循环即可检测到远程信号。该平台集成了遗传编码的压电或电动蛋白（例如，prestin变体）、细胞骨架张力调谐和基于超顺磁性氧化铁纳米粒子（SPIONs）的磁弹性纳米粒子谐振器，以在外磁场下实现可控的定向超声脉冲。这种双模式架构-移动传感和锚定通信-支持分布式生物导航，细胞间信息传递和潜在的治疗驱动。该框架为未来的实验实现建立了可行性条件和设计参数。

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引用次数: 0

Sickle Cell Crisis – Home Oxygen in the Golden Half Hour, can prevent or stop a crisis, prevent complications and change the trajectory of disease 镰状细胞危机-家庭氧气在黄金半小时，可以预防或停止危机，防止并发症和改变疾病的轨迹

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-24 DOI: 10.1016/j.mehy.2025.111869

Sota Omoigui

Reversible sickle cells (RSC) can become irreversible sickle cells (ISC) after repeated episodes of sickling. The reversible sickle cells can revert to their original flexible discoid shape when reoxygenated, but repeated or prolonged sickling can damage the cell membrane and make it impossible for the cells to return to their normal shape, becoming irreversible sickle cells. In-hospital oxygen therapy administered when patients are in a sickle cell crisis does not stop a crisis and does not reduce the pain. This is because patients are already in an irreversible sickle cell crisis; the cells have undergone cell damage and can no longer be resuscitated with oxygen. These sickle cells obstruct blood flow and have to be destroyed by the body in a process of hemolysis or phagocytosis. Such process leads to the known complications of sickle cell crisis including organ damage and severe anemia. However if oxygen is administered at home in the early stages of a crisis, preferably the golden half hour (30 mins), when the sickle cells are still reversible, it can restore the sickle cells to their normal discoid shape and prevents them from progressing to a critical mass of irreversible sickle cells, wherein the sickle cell crisis becomes established and intractable. The efficacy of home oxygen therapy in preventing and aborting a crisis in the golden half hour is very promising. Aborting a crisis would reduce ischemic and hemolytic complications, therefore lowering disability and mortality rates. In addition, it will reduce health care costs associated with SCD.

可逆镰状细胞（RSC）可成为不可逆镰状细胞（ISC）反复发作后。可逆镰状细胞在复氧后可恢复到原来的柔韧性盘状，但反复或长时间的镰状细胞会损伤细胞膜，使细胞无法恢复到正常形状，成为不可逆镰状细胞。当病人处于镰状细胞危象时，在医院内进行氧气治疗并不能阻止危象，也不能减轻疼痛。这是因为患者已经处于不可逆转的镰状细胞危象中；这些细胞已经受损，不能再用氧气使其复苏。这些镰状细胞阻碍血液流动，必须在溶血或吞噬过程中被身体消灭。这一过程导致镰状细胞危象的已知并发症，包括器官损伤和严重贫血。然而，如果在危机的早期阶段，最好是黄金半小时（30分钟），当镰状细胞仍然可逆时，在家中给予氧气，它可以使镰状细胞恢复到正常的盘状形状，并防止它们发展到不可逆转的镰状细胞的临界质量，此时镰状细胞危机变得确定和难以控制。家庭氧疗在黄金半小时内预防和终止危机的效果是非常有希望的。中止危机将减少缺血性和溶血性并发症，从而降低致残率和死亡率。此外，它还将降低与SCD相关的卫生保健费用。

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引用次数: 0

Creatine insufficiency as an energetic amplifier of brainstem dysfunction in ME/CFS and long COVID 肌酸不足是ME/CFS和长COVID患者脑干功能障碍的能量放大器

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-24 DOI: 10.1016/j.mehy.2025.111868

Nikola Todorovic

引用次数: 0

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