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Chrono-regulation of AR-V7: A potential temporal driver of hormone resistance in prostate cancer? AR-V7的时间调节：前列腺癌激素抵抗的潜在时间驱动因素？
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-25 DOI: 10.1016/j.mehy.2025.111669
Ivan Bivolarski
{"title":"Chrono-regulation of AR-V7: A potential temporal driver of hormone resistance in prostate cancer?","authors":"Ivan Bivolarski","doi":"10.1016/j.mehy.2025.111669","DOIUrl":"10.1016/j.mehy.2025.111669","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"200 ","pages":"Article 111669"},"PeriodicalIF":2.1,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147554","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
Retroviral synergy in oncogenesis via additive and cooperative protein actions and cross-reactivity of antiretroviral therapy 逆转录病毒在肿瘤发生中的协同作用通过蛋白质的加法和协同作用以及抗逆转录病毒治疗的交叉反应性
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-24 DOI: 10.1016/j.mehy.2025.111667
Ante Tomasović
{"title":"Retroviral synergy in oncogenesis via additive and cooperative protein actions and cross-reactivity of antiretroviral therapy","authors":"Ante Tomasović","doi":"10.1016/j.mehy.2025.111667","DOIUrl":"10.1016/j.mehy.2025.111667","url":null,"abstract":"<div><div>The hypothesis of retroviral synergy in oncogenesis via additive and cooperative protein actions proposes that functionally similar proteins from different retroelements act additive and cooperative within host cells, enhancing the total protein expression of said retroelements. This in turn enhances expression of retroviral tumorigenic regulator proteins which promote transformation of normal cells into cancer cells, increased proliferation, inhibition of apoptosis, and enhanced immune evasion, thereby contributing to both cancer development and its persistence.</div><div>The cross-reactivity of antiretroviral therapy hypothesis proposes that anti-HIV drugs exert anticancer effects by inhibiting one or more retroviruses, or endogenous retroelements, that are active within cancer cells.</div><div>Targeting retroviral enzymes in cancer cells can serve as a viable therapeutic approach, warranting further investigation.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"200 ","pages":"Article 111667"},"PeriodicalIF":2.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137712","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
MicroRNA-146a-3p as an alternative to anti-IL-6 monoclonal antibody therapy: Intra-articular liposome delivery for osteoarthritis treatment MicroRNA-146a-3p作为抗il -6单克隆抗体治疗的替代方案：关节内脂质体递送治疗骨关节炎
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-20 DOI: 10.1016/j.mehy.2025.111666
Chang-Chin Wu , Yang Wei , Joanna Kolmas , Kai-Chiang Yang
{"title":"MicroRNA-146a-3p as an alternative to anti-IL-6 monoclonal antibody therapy: Intra-articular liposome delivery for osteoarthritis treatment","authors":"Chang-Chin Wu ,&nbsp;Yang Wei ,&nbsp;Joanna Kolmas ,&nbsp;Kai-Chiang Yang","doi":"10.1016/j.mehy.2025.111666","DOIUrl":"10.1016/j.mehy.2025.111666","url":null,"abstract":"<div><div>Interleukin-6 (IL-6) is a crucial inflammatory cytokine associated with chronic pain and cartilage degradation in osteoarthritis (OA). The binding of IL-6 to the IL-6 receptor (IL-6R) leads to homodimerization and the recruitment of glycoprotein 130 (gp130), subsequently activating the transcription factor signal transducer and activator of transcription 3 (STAT3) to initiate the downstream inflammatory cascade. Therefore, a therapy that targets the IL-6/IL-6R/STAT3 signaling axis shows promise for OA treatment. MicroRNAs (miRs) modulate messenger RNA in translational regulation, and dysregulation of miR-146a is noted in articular cartilage. In addition, miR-146a is also known to regulate IL-6 expression and affect OA-associated algesia. Bioinformatic analysis revealed that miR-146a-3p targets IL-6, IL-6R, gp130, and STAT3 simultaneously. Accordingly, we hypothesize that multipoint targeting the IL-6/IL-6R/STAT3 signaling axis through intra-articular injection of liposomal miR-146a-3p mimic might replace anti-IL-6 monoclonal antibody therapy and serve as a disease-modifying treatment for OA.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"200 ","pages":"Article 111666"},"PeriodicalIF":2.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123219","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
‘Hypercobalaminuria’ – Is urinary cobalamin loss a potential determinant of parenteral cobalamin (B12) efficacy in Pernicious Anaemia? “高钴胺血症”——尿中钴胺素的丢失是否可能影响肠外钴胺素（B12）治疗恶性贫血的疗效？
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-19 DOI: 10.1016/j.mehy.2025.111664
Andrew McCaddon , Ebba Nexo , Ralph Green , Kourosh R Ahmadi , Luciana Hannibal , Alfie Thain , Joshua W Miller
{"title":"‘Hypercobalaminuria’ – Is urinary cobalamin loss a potential determinant of parenteral cobalamin (B12) efficacy in Pernicious Anaemia?","authors":"Andrew McCaddon ,&nbsp;Ebba Nexo ,&nbsp;Ralph Green ,&nbsp;Kourosh R Ahmadi ,&nbsp;Luciana Hannibal ,&nbsp;Alfie Thain ,&nbsp;Joshua W Miller","doi":"10.1016/j.mehy.2025.111664","DOIUrl":"10.1016/j.mehy.2025.111664","url":null,"abstract":"<div><div>It is unknown why many patients with pernicious anaemia are satisfactorily treated with injections of hydroxocobalamin or cyanocobalamin every 1–3 months whereas others require far more frequent replacement regimens, sometimes even weekly. A substantial but inconstant fraction of an injected dose of cobalamin is excreted in the urine within 72 h of injection, with subsequent loss of variable smaller amounts. We hypothesize the existence of ‘hypercobalaminuria’, whereby increased urinary cobalamin losses constitute a currently unrecognized factor influencing treatment refractoriness in some individuals. The hypothesis is testable by comparing cobalamin urinary losses in patients needing frequent as opposed to 1–3-monthly injections of cobalamin to remain symptom free. It implies that ‘less-responsive’ patients are likely to have significant hypercobalaminuria.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111664"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105696","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
The transition from biology to phenomenology 从生物学到现象学的转变
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-19 DOI: 10.1016/j.mehy.2025.111665
Erling Mellerup
{"title":"The transition from biology to phenomenology","authors":"Erling Mellerup","doi":"10.1016/j.mehy.2025.111665","DOIUrl":"10.1016/j.mehy.2025.111665","url":null,"abstract":"<div><div>Biologically, consciousness may arise when integrated nerve activity from e.g., sensory brain areas interact with brain areas showing spontaneous nerve activity. It is hypothesized that phenomenologically, consciousness may arise when the spontaneously active nerve cells that are affected by the integrated nerve activity feel this influence. Being able to feel something may be an evolutionary and fundamentally new phenomenon. and be the transition from biology to consciousness.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111665"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090173","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
The Lazarus’ sign: A novel hypothesis on its hodology and neurophysiological mechanisms 拉撒路的标志：一个关于其药理和神经生理机制的新假说
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-19 DOI: 10.1016/j.mehy.2025.111659
Nicolas de Cesaro Schpchacki, Andressa Mayer, Francisco Martins Lamas, Helena Horta, Lisiê Valéria Paz, Régis Gemerasca Mestriner, Léder Leal Xavier
{"title":"The Lazarus’ sign: A novel hypothesis on its hodology and neurophysiological mechanisms","authors":"Nicolas de Cesaro Schpchacki,&nbsp;Andressa Mayer,&nbsp;Francisco Martins Lamas,&nbsp;Helena Horta,&nbsp;Lisiê Valéria Paz,&nbsp;Régis Gemerasca Mestriner,&nbsp;Léder Leal Xavier","doi":"10.1016/j.mehy.2025.111659","DOIUrl":"10.1016/j.mehy.2025.111659","url":null,"abstract":"<div><div>The Lazarus’ sign, characterized by respiratory thoracic movements and arm flexion, is a complex and primitive motor response observed exclusively in patients with brain death in ventilator support (1). Thus, Lazarus’ sign is a rare spinal reflex, generating movement solely using propriospinal structures and only occurs under certain circumstances concomitant with brain death: apnea testing, ventilator withdrawal, arterial hypotension, nociceptive stimuli, and passive neck flexion (2). The correlations between these circumstances and Lazarus’ sign and the spinal cord structures responsible for this reflex remains unclear. This article, revising previous studies, propose a hypothesis regarding the essentials of this sign. In summary, based on cervical spinal cord microanatomy and neurophysiology, we present a detailed description regarding how the depolarization of respiratory motor neurons, originally responsible for thoracic expansion movements, promoted by hypoxia, nociceptive stimuli and proprioception also induces activation of alpha and gamma motor neurons, responsible for bilateral arm flexion, generating all patterns observed in Lazarus sign.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111659"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117122","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
Calcium phosphate cement-magnesium alloy composite scaffold for diaphyseal fracture fixation: a hypothesis 磷酸钙水泥-镁合金复合支架用于骨干骨折固定：一种假设
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-19 DOI: 10.1016/j.mehy.2025.111661
Wenbo Guo , Xiaochun Liu , Jinjin Gao , Yongqi Dang , Fu Sun
{"title":"Calcium phosphate cement-magnesium alloy composite scaffold for diaphyseal fracture fixation: a hypothesis","authors":"Wenbo Guo ,&nbsp;Xiaochun Liu ,&nbsp;Jinjin Gao ,&nbsp;Yongqi Dang ,&nbsp;Fu Sun","doi":"10.1016/j.mehy.2025.111661","DOIUrl":"10.1016/j.mehy.2025.111661","url":null,"abstract":"<div><div>For the treatment of long bone diaphyseal fractures, traditional orthopedic implants have limitations such as stress shielding, non-degradability, and soft tissue damage. In this study, we proposed a hypothesis that a novel calcium phosphate cement (CPC)-magnesium alloy composite scaffold would be applicable to reduce stress shielding and enable personalized treatment through structural surface modification techniques. Its biodegradable property might eliminate the need for secondary surgeries, while the products of degradation would synergistically promote bone healing. A modified surgical approach was suggested to minimize medullary cavity expansion, reduce joint and soft tissue trauma, and shorten recovery time. This concept may offer a novel therapeutic strategy for diaphyseal fractures to alleviate patients’ physiological, psychological, and financial burdens. In the future, the research directions may involve interface reinforcement, dynamic in vivo degradation-osteogenesis matching, and clinical translation validation.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111661"},"PeriodicalIF":2.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090175","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
The potential mechanisms of pain relief in patients after percutaneous vertebroplasty: Intravertebral pressure release and peripheral nerve ablation 经皮椎体成形术后疼痛缓解的潜在机制：椎体内压力释放和周围神经消融
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-16 DOI: 10.1016/j.mehy.2025.111663
Jihong Jiang, Lei Zhou, Yong Tang, Changwei Chen, Yangsheng Wang
{"title":"The potential mechanisms of pain relief in patients after percutaneous vertebroplasty: Intravertebral pressure release and peripheral nerve ablation","authors":"Jihong Jiang,&nbsp;Lei Zhou,&nbsp;Yong Tang,&nbsp;Changwei Chen,&nbsp;Yangsheng Wang","doi":"10.1016/j.mehy.2025.111663","DOIUrl":"10.1016/j.mehy.2025.111663","url":null,"abstract":"<div><div>Percutaneous vertebroplasty (PVP) is a minimally invasive procedure widely used for the treatment of osteoporotic vertebral compression fractures (OVCFs). Despite its widespread application, the exact mechanisms underlying the pain relief observed after PVP remain unclear. Based on an extensive review of the current literature, we propose two potential mechanisms for pain relief after PVP: intravertebral pressure release and peripheral nerve ablation. High intravertebral pressures recorded in fractured vertebrae suggest a potential role in pain generation, which may be relieved by the injection of bone cement facilitating pressure reduction and stabilization. Additionally, the thermal and chemical properties of bone cement may contribute to peripheral nerve ablation, interrupting pain signaling pathways. These mechanisms are supported by evidence from biomechanical studies, histopathological examinations, and clinical observations. This hypothesis aims to provide a more comprehensive understanding of the pain relief achieved after PVP, facilitating future research and optimization of the procedure.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111663"},"PeriodicalIF":2.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071459","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
New contributions to the theory of air pressure regulation mechanisms in the middle ear: The Eustachian tube resting ventilation and mastoid core hypotheses 中耳气压调节机制理论的新贡献：咽鼓管静息通气和乳突核心假说
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-16 DOI: 10.1016/j.mehy.2025.111652
Jingjing Liu , Tingyan Wei , Yunfeng Wang
{"title":"New contributions to the theory of air pressure regulation mechanisms in the middle ear: The Eustachian tube resting ventilation and mastoid core hypotheses","authors":"Jingjing Liu ,&nbsp;Tingyan Wei ,&nbsp;Yunfeng Wang","doi":"10.1016/j.mehy.2025.111652","DOIUrl":"10.1016/j.mehy.2025.111652","url":null,"abstract":"<div><div>The mechanism underlying middle ear air pressure regulation remains unclear, and the intrinsic links between related middle ear disorders such as acute otitis media (AOM), chronic suppurative otitis media (CSOM), and otitis media with effusion (OME) have not been adequately elucidated. The possibility of mucus blanket bubble formation and connection in the Eustachian tube (ET) lumen, inflammation that can alter gas exchange in the middle ear fissure, potential presence of bacteria in OME, and the unique role of the mastoid in the treatment of CSOM support our hypothesis regarding resting ET ventilation and the mastoid core. We aimed to refine the current theory of middle ear air pressure regulation. The intrinsic connections between middle ear disorders, such as AOM, CSOM, and OME, can be more rationally explained through this hypothesis. Further, it also clarifies how inflammation, the mastoid, middle ear, and ET interact in these disorders.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"200 ","pages":"Article 111652"},"PeriodicalIF":2.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170677","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
Beyond HbA1c: Can mitochondrial function assessment enhance evaluation of exercise efficacy? 超越糖化血红蛋白：线粒体功能评估是否能提高运动效果的评估？
IF 2.1 4区 医学
Medical hypotheses Pub Date : 2025-05-15 DOI: 10.1016/j.mehy.2025.111657
Yu-Hsiang Lin , Jau-Yuan Chen , Ke-Hung Tsui
{"title":"Beyond HbA1c: Can mitochondrial function assessment enhance evaluation of exercise efficacy?","authors":"Yu-Hsiang Lin ,&nbsp;Jau-Yuan Chen ,&nbsp;Ke-Hung Tsui","doi":"10.1016/j.mehy.2025.111657","DOIUrl":"10.1016/j.mehy.2025.111657","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"199 ","pages":"Article 111657"},"PeriodicalIF":2.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090174","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
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