Medical hypotheses最新文献

{"title":"Potential role of microalgae in delaying early menarche in girls with central precocious puberty","authors":"Monica Gulati ,&nbsp;Bhupinder Kapoor ,&nbsp;Maritza Guerrero ,&nbsp;Dina Keumala Sari ,&nbsp;Gayani Imanthika Dias ,&nbsp;Ivan Salazar Chang ,&nbsp;Sachin Kumar Singh","doi":"10.1016/j.mehy.2026.111917","DOIUrl":"10.1016/j.mehy.2026.111917","url":null,"abstract":"<div><div>Central precocious puberty (CPP) in girls is characterized by an early onset of puberty. Premature thelarche occurring before age of 8 years in such cases is followed by onset of menarche in next 2–3 years. Though certain causative environmental, genetic and hormonal factors have been identified, the exact etiology remains largely elusive in many cases. A connection between gut microbiome (GM) and precocious puberty has been widely reported attributing it to the well-known gut-endocrine axis. Gut dysbiosis has been proposed as the “missing link” in idiopathic CPP (ICPP). Accordingly, biotherapeutic strategies such as probiotic therapy, fecal microbiota transplantation, and dietary interventions (e.g. phytoestrogens<!--> <!-->and polyphenols) have been successfully tried. Recent studies have identified microalgae as a sustainable source of high-quality protein, with a number of additional benefits. These are attributed to their demonstrated anti-inflammatory, antioxidant, and anticancer properties. Moreover, microalgae are widely reported to restore gut microbiome homeostasis by exerting dual probiotic and prebiotic functions and influencing sex hormone biotransformation. Their role in biotransformation of sex hormones, therefore, makes microalgae a suitable candidate for this role <em>per se</em>. By joining the pieces of these intricate clues, we hypothesize that inclusion of microalgae in diet represents future of nutritional interventions in ICPP. Recognition of ICPP by onset of thelarche will alert the parents, physicians and nutritionists. Inclusion of nutritional supplementation with microalgae after this, could offer a rational approach for delaying the oncoming onset of menarche in children with ICPP.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111917"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386131","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":"Osteoclasts may play key roles in initiating vascular calcification during atherosclerosis","authors":"Yuxiao Liu ,&nbsp;Jingqi Wu ,&nbsp;Jingrong Chen ,&nbsp;Hongmei Zhang ,&nbsp;Mingzheng Li","doi":"10.1016/j.mehy.2026.111928","DOIUrl":"10.1016/j.mehy.2026.111928","url":null,"abstract":"<div><div>Vascular calcification, characterized by the ectopic deposition of calcium and phosphate crystals or even bone-like tissue, is a major risk factor for cardiovascular diseases such as atherosclerosis. However, the explicit mechanism remains unsettled. Current research demonstrates that atherosclerotic vascular calcification is a form of extraskeletal ossification—an active, cell-mediated process that closely resembles bone from macroscopic features down to the nanoscale structure. The mechanism underlying atherosclerotic calcification may be remarkably similar to those regulating bone remodeling and biomaterials-induced heterotopic ossification. This similarity is notably evidenced by the presence of osteoclast-like cells within vascular plaques. Based on previous findings that osteoclasts play key roles in initiating biomaterial-induced heterotopic ossification, we hypothesize for the first time that osteoclasts formed within the vascular wall may act as an ‘initiating signal’ triggering the development of atherosclerotic vascular calcification. This perspective may open new avenues for research into atherosclerotic calcification and contribute to the future development of strategies for its prevention and treatment.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111928"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386087","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":"Myocardial cell-derived exosomal miR-155-5p promotes depressive disorders in CVD via microglial SIRT1 pathway","authors":"Meng Ning ,&nbsp;Zhibin Zhang ,&nbsp;Chenguang Zheng","doi":"10.1016/j.mehy.2026.111906","DOIUrl":"10.1016/j.mehy.2026.111906","url":null,"abstract":"<div><div>Patients with cardiovascular disease (CVD) commonly experience comorbid depression; however, the mechanistic pathways linking cardiac pathology to depressive symptoms remain poorly elucidated. Here, we propose a novel hypothesis: myocardial injury induces cardiomyocytes to secrete exosomes enriched in miR-155-5p. We posit that these cardiogenic exosomes can cross the blood–brain barrier, be selectively taken up by microglia, and subsequently suppress Sirtuin 1 (SIRT1) expression in these cells. SIRT1 downregulation may trigger microglial activation, promote neuroinflammation, and thereby contribute to the onset of depressive-like behaviors. This hypothesis is grounded in convergent lines of evidence: (i) miR-155-5p is consistently upregulated in both CVD patients and individuals with depression; (ii) bioinformatic analyses robustly predict SIRT1 as a direct, functionally relevant target of miR-155-5p; and (iii) preclinical studies demonstrate amelioration of depressive-like phenotypes following either inhibition of miR-155-5p or pharmacological activation of SIRT1. If experimentally validated, this exosome-mediated heart–brain axis would offer a mechanistically coherent framework for understanding CVD–depression comorbidity—and identify miR-155-5p and SIRT1 as promising candidates for diagnostic biomarkers and targeted interventions.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111906"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386086","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":"A novel strategy combining high-intensity interval training and exogenous ketone supplementation for obesity treatment","authors":"Jay Lee ,&nbsp;Zhaowei Kong ,&nbsp;Jinlei Nie","doi":"10.1016/j.mehy.2026.111925","DOIUrl":"10.1016/j.mehy.2026.111925","url":null,"abstract":"<div><div>High-intensity interval training (HIIT) and exogenous ketone supplementation (EKS) have individually demonstrated potential in addressing overweight and obesity, particularly through their effects on appetite regulation and dietary behavior. However, the therapeutic potential of EKS in obesity management remains underexplored, and how it interacts with HIIT remains unclear. We hypothesize that combining HIIT and EKS may have a synergistic effect through “Neurocognitive-Behavioral Mechanisms”. These mechanisms include direct effects on appetite-related brain pathways and indirect effects such as improvements in cognitive function that support healthier eating habits. Both HIIT and EKS may also increase levels of newly identified signaling compounds, such as lactate-phenylanine (Lac-Phe) and 3-β-hydroxybutyrate (BHB)-Phe, which have been linked to reduced food intake in animal studies. Importantly, the shared pathways through which HIIT and ketones enhance cognitive function suggest that future obesity treatments could focus on optimizing brain and metabolic health, rather than relying solely on calorie restriction, to improve long-term adherence. Further research should clarify the neurocognitive and metabolic pathways involved and examine the long-term impact of combined HIIT and EKS interventions. This conceptual framework offers a novel perspective on how brain and behavior interact in obesity and may guide the development of innovative lifestyle strategies.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111925"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386135","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":"The mechanical protector paradox: a hypothesis linking transition zone enlargement, urethral angle, and carcinogenesis via intraprostatic reflux","authors":"Yu-Hsiang Lin ,&nbsp;Po-Ting Lin ,&nbsp;Tzu-Chi Teng ,&nbsp;Yu-Ting Chen ,&nbsp;Chen-Pang Hou ,&nbsp;Jau-Yuan Chen ,&nbsp;Chien-Lun Chen","doi":"10.1016/j.mehy.2026.111922","DOIUrl":"10.1016/j.mehy.2026.111922","url":null,"abstract":"<div><div>The relationship between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remains paradoxical: both share inflammatory pathways, yet larger prostates often harbor less aggressive disease. This paradox may be explained by the mechanical interaction between the transition zone (TZ) and the peripheral zone (PZ). We hypothesize that urethral morphology, particularly a more acute prostatic urethral angle (PUA), acts as a primary biomechanical risk factor. A sharper urethral bend increases local hydrodynamic pressure and reflux potential, promoting the pro-inflammatory stimuli in the PZ. Conversely, we propose that progressive TZ enlargement acts as a “mechanical protector” against this insult. By compressing the PZ, the enlarging TZ narrows its ducts and reduces the intraprostatic reflux driven by the PUA. This effect attenuates the inflammatory microenvironment that drives malignant transformation. Integrating these factors, we propose a mechanical–inflammatory model in which prostate volume and urethral geometry jointly regulate intraprostatic inflammation. Integrating these factors, we propose a mechanical–inflammatory model in which prostate volume and urethral geometry jointly regulate intraprostatic inflammation. This hypothesis provides a unifying explanation for the inverse association between prostate size and cancer aggressiveness and suggests new imaging and mechanistic pathways for future investigations.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111922"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386134","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":"Cell psychology: a conceptual reinterpretation of cellular stress responses through cognitive and psychological analogies","authors":"Nalin Gümüşçü","doi":"10.1016/j.mehy.2026.111923","DOIUrl":"10.1016/j.mehy.2026.111923","url":null,"abstract":"<div><div>This hypothesis proposes that cells, much like psychological entities, display adaptive, emotion-like responses and decision-oriented behavioral patterns when confronted with internal or external stressors. Termed “cell psychology”, this framework suggests that biological stress, genomic instability, and environmental fluctuations elicit cellular reactions analogous to psychological states such as anxiety, fatigue, exhaustion, and self-preservation. Under adverse conditions, cells may adopt altruistic strategies—most notably apoptosis—to maintain tissue integrity, or shift toward narcissistic, competitive behaviors such as uncontrolled proliferation, immune evasion, and tumorigenesis. Mitochondrial dysfunction, oxidative stress, lysosomal impairment, and stress-induced epigenetic alterations represent molecular parallels of emotional collapse, maladaptation, and aging, reflecting a progressive loss of resilience and homeostatic regulation. Interpreting cellular behavior through a psychological lens offers a novel integrative perspective linking molecular biology, neuropsychology, systems biology, and artificial intelligence. Parallels between cellular decision-making networks and cognitive processes—including information processing, memory formation, pattern recognition, and threshold evaluation—indicate that core principles of adaptation may operate across multiple biological scales. Cells detect signals, integrate competing inputs, and generate context-dependent outcomes, resembling primitive forms of cognitive computation.</div><div>Within this conceptual framework, “cell psychology” provides a bottom-up model for understanding cooperation, communication failure, pathological deviation, and multicellular organization. Reframing cellular responses as rudimentary expressions of choice, memory, and strategic adaptation offers new avenues for interpreting aging, cancer progression, regenerative capacity, and emergent biological order. Ultimately, this hypothesis raises the possibility that foundational elements of cognition, resilience, and behavioral complexity may originate from the adaptive, information-processing capacities intrinsic to individual cells.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111923"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386084","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":"3D Doppler territorial vascular mapping as a prognostic tool in uterine EMV/AVM","authors":"Amin Abolhasani Foroughi ,&nbsp;Seyed Sina Dehghani","doi":"10.1016/j.mehy.2026.111927","DOIUrl":"10.1016/j.mehy.2026.111927","url":null,"abstract":"<div><div>Acquired Uterine Enhanced Myometrial Vascularity/Arteriovenous Malformation (EMV/AVM) is uncommon vascular abnormality that can occasionally lead to severe uterine bleeding. Current Doppler indices, such as peak systolic velocity and resistance index, have limited prognostic value. We suggest that assessment of the territorial vascular supply pattern, characterized by involvement of one or multiple uterine regions (anterior, posterior, right lateral, left lateral, and fundal), using three-dimensional (3D) Doppler imaging may serve as a prognostic indicator in the management of these patients. Complex vascular architecture with multiple feeding arteries or overlapping territories may predict persistent hemorrhage and a higher need for embolization, whereas single-territory involvement may indicate a greater chance of spontaneous regression. Incorporating 3D Doppler into diagnostic protocols could refine risk stratification, reduce unnecessary interventions, and ultimately improve reproductive outcomes. This hypothesis calls for observational studies integrating vascular territory mapping alongside current Doppler parameters to establish its predictive role in acquired EMV/AVM.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111927"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386091","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":"Post-menopause cardiovascular risk – lack of hormones or bleeding? – Increased blood viscosity due to cessation in menstrual bleeding","authors":"Erik Finlayson","doi":"10.1016/j.mehy.2026.111915","DOIUrl":"10.1016/j.mehy.2026.111915","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111915"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386092","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":"From cellular cognition to psychopathology: a three-level framework of biological decision-making","authors":"Gastón Lenin Nole Guerrero","doi":"10.1016/j.mehy.2026.111914","DOIUrl":"10.1016/j.mehy.2026.111914","url":null,"abstract":"<div><div>This article proposes a three-level framework for understanding biological decision-making. At Level 1, the cellular living system perceives its environment through metabolic signals and selects adaptive states within gene regulatory networks. At Level 2, the neuron—as an evolved living system—amplifies these capacities through adaptive dendritic processing; we propose that nervous system evolution follows a hierarchical principle where newer structures acquire regulatory control over older ones. At Level 3, neuronal groups operate as collective selection units whose behavior depends on the balance between subcortical driver circuits and cortical inhibitory circuits.</div><div>The central contribution is a framework with falsifiable predictions. Cortical inhibitory control may critically depend on two energetically demanding neuronal populations: fast-spiking parvalbumin-positive interneurons (PV + ) and prefrontal pyramidal neurons (PrN). We propose that these populations share convergent vulnerability. PV + interneurons require maintenance of ionic gradients and sustained high-frequency firing. Prefrontal pyramidal neurons appear to have evolved with a specialization toward lipid metabolism, consistent with TKTL1-linked findings; they also exhibit higher energy costs due to partial myelination, depend on external lipid supply whose relevance has been highlighted by brain lipidomics studies, and show preferential enrichment of the MCT2 transporter, which could be compatible with preferential use of monocarboxylates as physiological substrate.</div><div>Critically, the type of energy substrate—not just its quantity—may determine neuronal firing stability. Metabolic studies suggest that β-hydroxybutyrate is an efficient substrate for GABA synthesis in cultured GABAergic neurons, and that ketones may favor inhibitory firing patterns while glucose may favor excitatory patterns. When the living system cannot sustain inhibitory tone, subcortical circuits such as the nucleus accumbens may assume behavioral control, restricting behavior outside conscious control and generating self-maintained pathological patterns: hyperphagia, depressive rumination, compulsion, craving.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111914"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386132","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":"Could early-life caffeine exposure program preterm infants for later-life caffeine dependence? A mechanistic hypothesis","authors":"Çağrı Cumhur Gök ,&nbsp;Emrah Can","doi":"10.1016/j.mehy.2026.111921","DOIUrl":"10.1016/j.mehy.2026.111921","url":null,"abstract":"<div><div>Caffeine remains a primary therapeutic agent for apnea of prematurity and continues to improve respiratory stability and neurodevelopmental outcomes. Treatment occurs during a developmental window in which synaptic connectivity is rapidly expanding, receptor expression is shifting, and neuromodulatory systems are establishing long-term regulatory patterns. During this period, the maturation of A1 and A2A receptors influences neuronal excitability, sleep–wake organization, and endogenous protective mechanisms. Experimental studies demonstrate that neonatal caffeine exposure modifies A1 receptor ontogeny, alters ligand sensitivity, and induces lasting changes in ventilatory control. Considering the functional interaction between A2A and dopamine D2 receptors in striatal pathways, early adenosine antagonism may also influence the developmental calibration of reward circuitry.</div><div>Animal data consistently show that neonatal caffeine exposure produces behavioral and neuromodulatory alterations that persist into later life, affecting motor activity, sleep organization, memory performance, and responsiveness to stimulant agents. Human studies, however, have not assessed reward sensitivity, stimulant responsivity, or caffeine-use patterns in individuals born preterm, leaving an important developmental gap. These observations support a biologically grounded hypothesis: early-life caffeine therapy may shift the maturation of arousal and reward systems in ways that shape later susceptibility to altered caffeine sensitivity or reinforcement patterns. If this connection is confirmed, clinical approaches may need to reconsider dosing strategies and broaden long-term follow-up to include behavioral and neurophysiological assessments in former preterm infants treated with caffeine.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111921"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386088","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}