[
  {
    "pmid": "31717265",
    "title": "Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?",
    "journal": "Nutrients",
    "year": "2019",
    "doi": "10.3390/nu11112704",
    "abstract": "Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood-brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood-brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review."
  },
  {
    "pmid": "34084149",
    "title": "Leptin and Obesity: Role and Clinical Implication.",
    "journal": "Frontiers in endocrinology",
    "year": "2021",
    "doi": "10.3389/fendo.2021.585887",
    "abstract": "The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese ( ob ) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin's pleiotropic effects, playing a crucial role in regulating body mass  via  a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment."
  },
  {
    "pmid": "32230973",
    "title": "Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources.",
    "journal": "Molecules (Basel, Switzerland)",
    "year": "2020",
    "doi": "10.3390/molecules25071537",
    "abstract": "Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms."
  },
  {
    "pmid": "37432655",
    "title": "Melanin: insights into structure, analysis, and biological activities for future development.",
    "journal": "Journal of materials chemistry. B",
    "year": "2023",
    "doi": "10.1039/d3tb01132a",
    "abstract": "Melanin, a widely distributed pigment found in various organisms, possesses distinct structures that can be classified into five main types: eumelanin (found in animals and plants), pheomelanin (found in animals and plants), allomelanin (found in plants), neuromelanin (found in animals), and pyomelanin (found in fungi and bacteria). In this review, we present an overview of the structure and composition of melanin, as well as the various spectroscopic identification methods that can be used, such as Fourier transform infrared (FTIR) spectroscopy, electron spin resonance (ESR) spectroscopy, and thermogravimetric analysis (TGA). We also provide a summary of the extraction methods of melanin and its diverse biological activities, including antibacterial properties, anti-radiation effects, and photothermal effects. The current state of research on natural melanin and its potential for further development is discussed. In particular, the review provides a comprehensive summary of the analysis methods used to determine melanin species, offering valuable insights and references for future research. Overall, this review aims to provide a thorough understanding of the concept and classification of melanin, its structure, physicochemical properties, and structural identification methods, as well as its various applications in the field of biology."
  },
  {
    "pmid": "4581204",
    "title": "Adrenochrome and related compounds.",
    "journal": "Progress in medicinal chemistry",
    "year": "1972",
    "doi": "10.1016/s0079-6468(08)70401-6",
    "abstract": ""
  },
  {
    "pmid": "14130059",
    "title": "THE ADRENOCHROME THEORY OF SCHIZOPHRENIA: A REVIEW.",
    "journal": "Diseases of the nervous system",
    "year": "1964",
    "doi": "",
    "abstract": ""
  },
  {
    "pmid": "39953524",
    "title": "Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial.",
    "journal": "Journal of translational medicine",
    "year": "2025",
    "doi": "10.1186/s12967-025-06215-w",
    "abstract": "Preclinical evidence suggests that young plasma has beneficial effects on multiple organ systems in aged mice. Whether young plasma exerts beneficial effects in an aging human population remains highly controversial. Despite lacking data, young donor plasma infusions have been promoted for age-related conditions. Given the preclinical evidence that young plasma exerts beneficial effects by attenuating inflammation, this study examined whether administering a young plasma protein fraction to an elderly population would exert anti-inflammatory and immune modulating effects in humans, using surgery as a tissue injury model. This double-blind, placebo-controlled study enrolled and randomized 38 patients undergoing major joint replacement surgery. Patients received four separate infusions of a plasma protein fraction derived from young donors, or placebo one day before surgery, before and after surgery on the day of surgery, and one day after surgery. Blood specimens for proteomic and immunological analyses were collected before each infusion. Based on the high-content assessment of circulating plasma proteins with single-cell analyses of peripheral immune cells, proteomic signatures and cell-type-specific signaling responses that separated the treatment groups were derived with regression models. Elastic net regression models revealed that administration a young plasma protein fraction significantly altered the proteomic (AUC\u2009=\u20090.796, p\u2009=\u20090.002) and the cellular immune response (AUC 0.904, p\u2009<\u20090.001) to surgical trauma resulting in signaling pathway- and cell type-specific anti-inflammatory immune modulation. Affected proteomic pathways regulating inflammation included JAK-STAT, NF-kappa B, and MAPK (p\u2009<\u20090.001). These findings were confirmed at the cellular level as the MAPK and JAK/STAT signaling responses were diminished and IkB, the negative regulator of NFkB, was elevated in adaptive immune cells. Reported findings provide a first proof of principle in humans that a young plasma protein fraction actively regulates inflammatory and immune responses in an elderly population. They provide a solid rationale for elucidating active principles in young plasma that may be of therapeutic benefits for a range of age-related pathologies. ClinicalTrials.gov, NCT03981419."
  },
  {
    "pmid": "27732721",
    "title": "Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.",
    "journal": "JAMA",
    "year": "2016",
    "doi": "10.1001/jama.2016.9185",
    "abstract": "More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain. To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion. Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12\u202f587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes. It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence). Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued."
  },
  {
    "pmid": "33573745",
    "title": "Leptin in Leanness and Obesity: JACC State-of-the-Art Review.",
    "journal": "Journal of the American College of Cardiology",
    "year": "2021",
    "doi": "10.1016/j.jacc.2020.11.069",
    "abstract": "Leptin has emerged over the past 2 decades as a key hormone secreted by adipose tissue that conveys information on energy stores. Leptin is considered an important regulator of both neuroendocrine function and energy homeostasis. Numerous studies (mainly preclinical and much less in humans) have investigated the mechanisms of leptin's actions both in the healthy state as well as in a wide range of metabolic diseases. In this review, the authors present leptin physiology and review the main findings from animal studies, observational and interventional studies, and clinical trials in humans that have investigated the role of leptin in metabolism and cardiometabolic diseases (energy deficiency, obesity, diabetes, cardiovascular diseases, nonalcoholic fatty liver disease). The authors discuss the similarities and discrepancies between animal and human biology and present clinical applications of leptin, directions for future research, and current approaches for the development of the next-generation leptin analogs."
  },
  {
    "pmid": "5389100",
    "title": "Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein).",
    "journal": "The Journal of biological chemistry",
    "year": "1969",
    "doi": "",
    "abstract": ""
  }
]