Yale Journal of Biology and Medicine最新文献

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID, represents a significant and complex health challenge with a wide range of symptoms affecting multiple organ systems. This review examines the emerging evidence suggesting a critical role of the gut and gut-brain axis in the pathophysiology of Long COVID. It explores how changes in the gut microbiome, disruption of gut barrier integrity, and the persistence of SARS-CoV-2 antigens within the gastrointestinal tract may contribute to the prolonged and varied symptoms seen in Long COVID, including chronic inflammation and neuropsychiatric disturbances. The review also summarizes key insights gained about Long COVID, highlighting its multifactorial nature, which involves immune dysregulation, microvascular damage, and autonomic nervous system dysfunction, with the gut playing a central role in these processes. While progress has been made in understanding these mechanisms, current evidence remains inconclusive. The challenges of establishing causality, standardizing research methodologies, and addressing individual variations in the microbiome are discussed, emphasizing the need for further longitudinal studies and more comprehensive approaches to enhance our understanding of these complex interactions. This review underscores the importance of personalized approaches in developing effective diagnostic and therapeutic strategies for Long COVID, while also acknowledging the significant gaps in our current understanding. Future research should aim to further unravel the complex interplay between the gut and Long COVID, ultimately improving outcomes for those affected by this condition.

In relation to ancient infections, a substantial number of retroviral sequences with persistent immunogenic potential were integrated within the human genome (HERVs). Under physiological conditions, coding sequences from HERVs can participate in cell/tissue homeostasis and physiological functions in an epigenetically controlled manner. However, HERV expression is susceptible to contribute to various pathologies, including autoinflammatory and autoimmune disorders, when reprogrammed by exogenous stimuli such as drugs or microbial infections. Both innate and adaptive components of the immune system can be mobilized in response to deregulated/de-repressed expression of HERV determinants and thereby, modify immune tolerance to tissue antigens. Self-directed immune responses induced/worsened by HERV expression are suspected to participate in both tissue-specific and systemic disorders. A substantial level of mechanistic investigation is needed to better delineate the impact of HERV expression in diseases in general, and in inflammation and autoimmunity in particular.

Ocular gene therapy has rapidly advanced from proof-of-concept studies to clinical trials by exploiting the unique advantages of the eye, including its easy accessibility, relative immune privilege, and the ability to use the contralateral eye as a control. An important step forward was achieved with the Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna) for the treatment of biallelic RPE65-mutation-associated retinal dystrophies in 2017. Gene therapy is a promising field aimed at treating various inherited and acquired eye diseases. Viral vectors such as adeno-associated virus (AAV) are mainly used to efficiently deliver genes. Despite the immune-privileged status of the eye, viral vector-based therapies can induce immune responses, potentially leading to gene therapy-associated uveitis. Future directions include developing strategies to reduce immune responses while maintaining therapeutic efficacy, optimizing vector selection, and improving delivery techniques. Continued advances in the field of viral vectors, particularly AAV, are expanding the potential applications of gene therapy to treat a variety of ocular diseases. To fully realize the potential of ocular gene therapy, more research and clinical trials are needed to improve these methods, ensure safe and efficient treatments, and ultimately overcome existing obstacles.

The Coronavirus Disease 2019 (COVID-19) pandemic, driven by the novel coronavirus and its variants, has caused over 518 million infections and 6.25 million deaths globally, leading to a significant health crisis. Beyond its primary respiratory impact, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been implicated in various extra-pulmonary complications. Research studies reveal that the virus affects multiple organs, including the kidneys, liver, pancreas, and central nervous system (CNS), largely due to the widespread expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors. Clinical evidence shows that the virus can induce diabetes by disrupting pancreatic and liver functions as well as cause acute kidney injury. Additionally, neurological complications, including cognitive impairments and neuroinflammation, have been observed in a significant number of COVID-19 patients. This review discusses the mechanisms linking SARS-CoV-2 to acute kidney injury, Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM), emphasizing its effects on pancreatic beta cells, insulin resistance, and the regulation of gluconeogenesis. We also explore how SARS-CoV-2 induces neurological complications, detailing the intricate pathways of neuro-invasion and the potential to trigger conditions such as Alzheimer's disease (AD). By elucidating the metabolic and neurological manifestations of COVID-19 and the underlying pathogenic mechanisms, this review underscores the imperative for continued research and the development of effective therapeutic interventions to mitigate the long-term and short-term impacts of SARS-CoV-2 infection.

Depression is a significant mental health challenge globally. While traditional antidepressants are effective, they often have unwanted side effects. Saffron, a natural spice derived from Crocus sativus L., has emerged as a potential alternative therapy for depression. Researchers have found that its components such as crocin, crocetin, and safranal have been found to mitigate depressive symptoms through neurotransmitter regulation, anti-inflammatory effects, and neuroprotection. Clinical trials suggest that the effectiveness of saffron in treating mild to moderate depression is comparable to that of standard medications, and animal studies support these results, showing behavioral improvements with saffron treatment. Saffron is particularly appealing due to its safety and lower incidence of side effects, making it suitable for those sensitive to conventional drugs. Additionally, its antioxidant properties may offer further health benefits. However, challenges such as determining the appropriate dosage, prohibitive cost, and the limited availability of quality saffron need to be addressed. Most research on saffron's efficacy is short-term; thus, long-term studies are essential to understand its full therapeutic potential and ongoing antidepressant effects. While saffron is safe in terms of its culinary value, higher therapeutic doses require careful monitoring for drug interactions and side effects. In summary, saffron represents a promising direction in depression treatment, with benefits potentially matching those of standard treatments and a better safety profile. However, further research is necessary to establish clear guidelines for its use, optimize dosing, and assess long-term outcomes. Saffron offers a natural treatment path for depression, but its use must be controlled and supported by scientific evidence.

Background: The musculoskeletal system, due to inherent structure and function, lends itself to contributing toward joint pain, whether from inflammatory disorders such as rheumatoid arthritis, degenerative diseases such as osteoarthritis, or trauma causing soft tissue injury. Administration of peptides for treatment of joint pain or inflammation is an emerging line of therapy that seeks to offer therapeutic benefits while remaining safe and relatively non-invasive. Purpose: The purpose of this study is to review the current literature on existing oral peptide agents, intra-articular peptide agents, and new developments in human trials to assess route of administration (RoA) for drug delivery in terms of soft tissue regeneration. Study Design: Narrative Review. Methods: A comprehensive literature search was conducted using the PubMed database. The search included medical subject headings (MeSH) terms related to peptide therapy, soft tissue regeneration, and RoA. Inclusion criteria comprised articles focusing on the mechanisms of action of peptides, clinical or biochemical outcomes, and review articles. Exclusion criteria included insufficient literature or studies not meeting the set evidence level. Conclusion: The review identified various peptides demonstrating efficacy in soft tissue repair. Oral and intra-articular peptides showed distinct advantages in soft tissue regeneration, with intra-articular routes providing localized effects and oral routes offering systemic benefits. However, both routes have limitations in bioavailability and absorption. Still in their infancy, further inquiries/research into the properties and efficacy of emerging peptides will be necessary before widespread use. As a viable alternative prior to surgical intervention, peptide treatments present as promising candidates for positive outcomes in soft tissue regeneration.

Background: Drug therapies have been widely applied for pain management, however, there are important side effects such as those related to corticosteroids and opioids. Recent studies demonstrated promising results using medical ozone as a safe, effective, and low-cost intervention for pain control. Objective: to review and critically analyze clinical studies that used ozone therapy for musculoskeletal pain. Methods: a literature search of various databases was performed to identify relevant studies. From a total of 249 records, 27 studies were included. Quality indicators, human and device factors that strongly influence the generation of evidence were considered, such as study design and device safety. We also mitigated biases, considering the safety and efficacy of the intervention itself. Results: Regarding safety, 77 (8%) of studies reported no adverse effects; concerning efficacy outcomes, medical ozone shows to be an effective intervention on musculoskeletal pain control. Important information about used devices were missing. Conclusions: medical ozone shows to be safe and effective; qualification of health professionals as well as the device safety are mandatory. However, there is a lack of requirements to identify the best therapeutic scheme; further longer, clinical and rigorous trials are needed.

In modern healthcare, the influence of a patient's mindset on health outcomes is an often neglected yet vital component of holistic care. This review explores the significant impact of positive and negative mindsets on disease progression and recovery, emphasizing the need to integrate mental wellness practices into conventional medical care. Drawing from a wide array of studies, it demonstrates how fostering a positive mindset can enhance patient trajectories across various medical specialties. The article advocates for training healthcare providers to adopt a more empathetic and patient-centered approach, bridging the gap between mind and body. By presenting compelling evidence on the correlation between patient mindset and health outcomes, this review highlights the potential benefits of incorporating psychological support and holistic strategies into standard care protocols. Practical strategies for implementing mindset-focused interventions are also proposed, including training programs for healthcare professionals and the development of interdisciplinary treatment plans. Ultimately, this article underscores the need for a paradigm shift in medical practice, advocating for a comprehensive approach that recognizes the power of thought in promoting patient wellness.

Objective: To identify factors impacting survivorship among people living with spinal cord injury (SCI) and volunteering in a peer mentorship program. Research Method/Design: Semi-structured interviews were conducted by a leader of a non-profit organization designed to promote independent living after SCI. Questions explored intrinsic factors such as resilience and emotional coping as well extrinsic factors such as family support and accessibility challenges that impacted their SCI survivorship journey. Two independent anonymous reviewers conducted thematic analysis to identify these factors. Results: Twenty-eight members of the SCI peer mentorship program participated. Four themes affecting survivorship were identified: Sense of Achievement, Post-Injury Growth, Post-Injury Challenges, and Giving and Receiving Support. Nearly all participants focused their responses on Post-Injury Growth and Giving and Receiving Support as reasons for their interest in serving as peer mentors. Conclusions: This study highlights a need for peer community integration following SCI and underscores the importance of using a community-driven participatory model to inform and guide research. Peer mentorship programs can link SCI survivors to mentors and facilitate other sources of social fulfillment and thus can have a profound impact on individuals' survivorship post-SCI. This study identified a Sense of Achievement, Post-Injury Growth, Giving and Receiving Support, and Post-Injury Challenges as factors that most impact the SCI survivorship journey. This community leader's work underscores the importance of cognitive framing and social networks in post-injury rehabilitation in this population. Future directions include analyzing the longitudinal effects of peer mentorship participation on life satisfaction and community building in individuals living with SCI.

The gut microbiota is a very important factor in the state of health of an individual, its alteration implies a situation of "dysbiosis," which can be connected to functional gastrointestinal disorders and pathological conditions, such as Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), Ulcerative Colitis (UC) and Crohn's Disease (CD), and Colorectal Cancer (CRC). In this work, we studied the effect of a food supplement called ENTERO-AD containing a mix of probiotics (Lactobacillus acidophilus LA1, L. reuteri LR92, Bifidobacterium breve Bbr8), Matricaria Chamomilla, and B group vitamins (B1, B2, B6) on intestinal inflammation. The in vitro model used for the study is the Caco-2 cell, a culture derived from human intestinal adenocarcinoma; the inflammatory condition was achieved with treatment with Lipopolysaccharide (LPS) and the association between Tumor necrosis factor α/Interferon γ (TNF-α/IFN-γ) [1,2]. The effect of ENTERO-AD was evaluated by cell viability, measures of Transepithelial Electrical Resistance (TEER), paracellular permeability, and immunofluorescence. Results of the study have shown that ENTERO-AD has a favorable effect on Caco-2 cells in inflammatory conditions. It improves the integrity of Occludin and Zonula Occludens-1 (ZO-1) proteins, leading to an improvement in terms of TEER values and a reduction of paracellular permeability. This evidence underlines the protective effect of ENTERO-AD and its components in intestinal inflammation.