Medical hypotheses最新文献

Primary Sjogren’s syndrome (pSS) is a systemic autoimmune inflammatory disease characterized by xerophthalmia and xerostomia, leading to a notable decline in patients’ quality of life. Recent studies have shown a link between the autonomic nervous system (ANS) dysfunction and pSS. The salivary and lacrimal glands are innervated by both sympathetic and parasympathetic nerves, highlighting the role of the ANS. Stellate ganglion block (SGB), a commonly used nerve block technique in clinical settings, exhibits the ability to modulate both the ANS and the immune response. Therefore, our hypothesis suggests that SGB may alleviate xerostomia and xerophthalmia in pSS patients through a short-term mechanism involving the adjustment of ANS balance and vasodilation to facilitate glandular secretion. Additionally, the long-term efficacy of SGB in pSS may be attributed to its neuroimmunomodulatory effects. Furthermore, it is likely that SGB could also improve a variety of ANS-related extra-glandular symptoms in pSS, including digestive, cardiovascular, neurological, and psychological issues.

Spina bifida is one of the most common developmental fetal malformations. It is a defect in dorsal spinal elements that exposes nerve tissue to the external environment – the amniotic fluid – leading to toxic exposure. By reviewing the development of fetal therapy, the physiopathology, and the mechanism of spina bifida, we hypothesize that the repetitive early replacement of the amniotic fluid with lactated Ringer’s solution via amnioinfusion may reduce toxicity to the exposed nerve tissue. Studies in fetal rat models suggest that amniotic fluid is toxic to the exposed spinal cord by an inflammatory response. Given the similarity between lactated Ringer’s solution and amniotic fluid, this replacement could mitigate toxicity without altering the intrauterine environment. Randomized controlled trials in animals and human fetuses are needed to test this hypothesis. If effective, this approach could benefit conservative couples and be applicable in low-income settings, improving outcomes after fetal surgery.

Lipid droplets (LDs) accumulation in cancer cells has garnered attention due to their role in tumor progression. Cholesterol supports not only the biosynthesis of new membranes and cancer-associated signaling but also modulate tumor cell energy supply which makes it therapeutically promising to target cholesterol metabolism. We hypothesize that autophagy-modulated inhibition of cholesterol uptake will reduce LDs formation and impair tumor progression via a novel pathway. The proposed approach has promise in disrupting cancer cell progression via impairing autophagy-mediated cholesterol uptake and few other metabolic processes. We emphasize investigating these mechanisms as they could significantly advance cancer therapy via targeting cholesterol metabolism and autophagy.

Warts are a common skin complaint caused by viral infections. Cryotherapy is a well-established approach for wart removal, which apply low temperatures to freeze and destroy infectious cells. However, this process may face-up several unwanted side effect on healthy nearby tissues. Besides, proper penetration of such temperature is also required to cause irreversible damages in deep-root infectious layers. In this respect, ice-producing proteins that are naturally found in some bacterial species, knowing as ice nucleation active (INA) bacteria, may be practical. In the current work, we hypothesized purification and encapsulation of these proteins into vesicular lipid particles (such as liposomes, niosomes, and exosomes) for an intralesional injection. Thereby, effective wart removal would be achieved even at low temperatures without undesirable effects.

This study establishes a hypothesis on cerebral venous thrombosis (CVT)-induced intracerebral hemorrhage (ICH), emphasizing distinctive computer tomography (CT) imaging features indicative of venous origin hemorrhages—characterized by lower CT values, diffuse cloud-like appearances, and indistinct borders, attributed to the dynamics of venous bleeding and plasma-dominated blood composition. It further delineates the unique propagation pattern of venous ICH, favoring slow diffusion through white matter tracts rather than entering sulci or breaching the arachnoid membrane, and highlights the susceptibility of specific brain regions due to their venous architecture. Contrasting these findings with arterial ICH, the paper argues for the need for tailored diagnostic and therapeutic approaches. It concludes with a discussion on future research directions, focusing on the development of novel diagnostic tools and treatment modalities specific to venous ICH.

Kashin-Beck disease (KBD) is a prevalent, endemic, and degenerative cartilage injury disorder, characterized by high rates of teratogenicity and disability. The etiology and pathogenesis of KBD are not fully understood, although research suggests that selenium deficiency and exposure to T-2 toxin are significant environmental risk factors. The initial pathological changes of KBD manifest as necrosis of deep chondrocytes, dedifferentiation of chondrocytes, excessive apoptosis of chondrocytes, and subsequent disruption of extracellular matrix metabolism. However, the precise pathogenic mechanisms of chondrocyte damage in KBD remain incompletely understood. Ferroptosis is a unique form of programmed cell death triggered by iron-dependent lipid peroxide accumulation. It has been shown to contribute to cartilage damage and chondrocyte death in various osteoarticular conditions, particularly osteoarthritis (OA). Notably, KBD not only exhibits clinical and pathological similarities with OA, but also indicates a potential association with ferroptosis in morphological and molecular similarities. Additionally, the environmental risk factors T-2 toxin exposure and selenium deficiency are also significant contributors to ferroptosis. Consequently, it is plausible to postulate that environmental risk factors may trigger ferroptosis, leading to the initiation of cartilage damage in KBD. Our hypothesis can be verified through both in vitro and in vivo experiments. Chondrocyte injury induced by ferroptosis may be a novel finding in KBD, which is important for clarifying its etiology and developing effective therapeutic strategies.

Social stress (SS) can lead to mental disorders (MD) in some people, such as depression and anxiety, while others who are resilient can handle SS without showing signs of mental illness. Resilience is characterized by human capacity to adapt to life’s adverse events without losing function or developing a mental disorder. Exploring molecular processes can help elucidate resilience mechanisms that counteract the pathophysiology of depression. Gut microbiome plays an essential role in the homeostasis of human body, especially the central nervous system (CNS). Therefore, it may support the counterbalance of certain disorders, such as depression, through the microbiota-gut-brain (MGB) axis. Short-chain fatty acids (SCFAs) produced by the gut microbiota, such as butyrate, increase the transmission activity of neurotransmitters, brain-derived neurotrophic factor (BDNF) expression and the regulation of microglia maturation enhances resilience in response to stress. Probiotics can be engineered to yield more butyrate. However, the overproduction of SCFAs is not necessarily beneficial and may lead to known side effects, such as intestinal dysbiosis or metabolic dysfunction. Herein, as we hypothesized the potential effect of the microbiome in resilience promotion, we have designed a cortisol-sensitive operon that allows gut microbiota to regulate the production of SCFAs according to the environmental demands which produces butyrate only when responding to stress. Amongst gut bacteria, Faecalibacterium prausnitzii (F. prausnitzii) has large amounts of butyrate and can be manipulated by designed plasmid, a process which makes it a suitable candidate to be translated into clinic.

Respiration involves the inspiration of atmospheric gases. Arguments are put forth that it is not oxygen gas that passes from the alveoli to the capillaries, but electrons extracted from the oxygen. Those electrons are theorized to bind to hemoglobin. They are then passed by the circulation directly to the tissues, where they support metabolism. Issues confronting the standard respiratory paradigm are identified, while various observations are put forth that seem consistent with the direct role of electrons in the respiratory process. If the hypothesis is validated, then a direct link will have been established between respiration and metabolism.

Robotic-assisted mitral valve surgery is gaining renewed popularity in the global surgical community. Appropriate patient-specific planning is pivotal for the safety and effectiveness of this procedure. One main step in this perspective is represented by the choice of placement of four ports in the right chest, for the introduction of robotic arms. Individual anatomical features (e.g., chest morphology and position of the mitral valve inside the chest) may determine inadequate surgical exposure, conversion to open procedure, or refusal for the technique. Currently, and contrary to robotic-assisted procedures in other surgical specialties, there is no dedicated approach or tool for patient-specific planning aimed at formally addressing these issues preoperatively. Herein, we present a dedicated, comprehensive method entailing: a homemade algorithm for rib segmentation (deep learning approach) and identification of intercostal spaces / candidate port entry sites; semiautomatic definition of a target working volume (mitral valve); definition of dedicated Performance Measure J* based on each potential triad of thoracic ports entry sites. We propose the dedicated J* parameter to better indicate the optimal patient-specific entry port solution than other parameters (h_e, ic, CCI and E). Prospective clinical studies should be based on the J* parameter. We hypothesize that this approach, dedicated to the requirements of robotic-assisted mitral valve surgery, may enhance the safety and the diffusion of this surgical strategy.