Physiological Role Research Articles

Hydrogen Sulfide: Physiological Roles and Therapeutic Implications against COVID-19.

The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-- COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.

Finding the Optimal Strategy for Nonculprit Revascularization in Acute Myocardial Infarction: The Role of Angiography-Derived Physiology.

Finding the Optimal Strategy for Nonculprit Revascularization in Acute Myocardial Infarction: The Role of Angiography-Derived Physiology.

Predictive Role of Acute Physiology and Chronic Health Evaluation II (APACHE II) in Patients With Peritonitis at the National Hospital Abuja.

A validated tool may facilitate assessing the severity of peritonitis among surgical patients. This study evaluates the predictive role of Acute Physiology and Chronic Health Evaluation II (APACHE II) in the surgical outcomes of patients managed for peritonitis in Abuja. This is a prospective study of consecutive adult patients managed for peritonitis by the general surgery unit of National Hospital Abuja (NHA) over a 19-month period (September 2020 through March 2022). Patient characteristics and treatment outcomes were recorded in a structured proforma and analyzed using SPSS Statistics version 25 (IBM Corp., Released 2017; IBM SPSS Statistics for Windows, Version 25.0; Armonk, NY: IBM Corp.). The accuracy, sensitivity, specificity, and threshold of APACHE II were derived from the receiver operating characteristic (ROC) curve analysis and its coordinates. There were 54 patients with peritonitis during the study period, with a male-to-female ratio of 2.6:1. This study's mortality and morbidity rates were 13.0% and 63.0%, respectively. The APACHE II score at admission was positively correlated with the likelihood of postoperative mortality, morbidity, number of postoperative complications, ICU admission, and length of hospital admission. The average APACHE II score of patients in this study was 7.1±5.2. APACHE II best-predicted mortality by the ROC curve at a threshold point of 9 (sensitivity of 85.7%, specificity of 70.2%, the accuracy of 86.8%, P-value 0.002). At a threshold score of 6, APACHE II was significantly associated with the occurrence of postoperative morbidity (sensitivity of 74.3%, specificity of 73.7%, accuracy of 75.2%, P-value = 0.043). This study confirms that the APACHE II score at admission can predict the outcome of surgery within the first 30 days post-surgery among adult patients who had peritonitis at NHA.

Redefining Classical Theory of Humours (Akhlat) with Emphasis on Khilt-e-Sauda (Black Bile) Through its Physiological Role

Background: According to Hippocrates, Akhlat is of four types, i.e., Dam (Blood), Balgham (Phlegm), Safra (Yellow Bile), and Sauda (Black Bile). The correct proportion of these fluids in the body, in terms of quality and quantity, leads to health, while their irregular distribution leads to diseases. The argument presented in this paper will encompass both Tabayi and Ghair Tabayi Sauda. Objective: However, in light of recent advances in the area of molecular biology and biochemistry of the human body, we aim to discuss Sauda as a Khilt in the context of human physiology. We propose that the chemico-biological / physiological role of the molecule rather than its structure will define its placement in Khilt-e-Sauda. Conclusion: Chemico/biological role of the molecule may change with the physiological context, and hence the placement of the molecule previously included in the Khilt-e-Sauda, may or may not remain in that categorization at that point in time in that physiological state.

Thermal tolerance does not explain the altitudinal segregation of lowland and alpine aquatic insects

Elevation gradients provide powerful study systems for examining the influence of environmental filters in shaping species assemblages. High-mountain habitats host specific high-elevation assemblages, often comprising specialist species adapted to endure pronounced abiotic stress, while such harsh conditions prevent lowland species from colonizing or establishing. While thermal tolerance may drive the altitudinal segregation of ectotherms, its role in structuring aquatic insect communities remains poorly explored. This study investigates the role of thermal physiology in shaping the current distribution of high-mountain diving beetles from the Sierra Nevada Iberian mountain range and closely related lowland species. Cold tolerance of five species from each altitudinal zone was measured estimating the supercooling point (SCP), lower lethal temperature (LLT) and tolerance to ice enclosure, while heat tolerance was assessed from the heat coma temperature (HCT). Alpine species exhibited wider fundamental thermal niches than lowland species, likely associated with the broader range of climatic conditions in high-mountain areas. Cold tolerance did not seem to prevent lowland species from colonizing higher elevations, as most studied species were moderately freeze-tolerant. Therefore, fundamental thermal niches seem not to fully explain species segregation along elevation gradients, suggesting that other thermal tolerance traits, environmental factors, and biotic interactions may also play important roles.

Amyloid precursor protein combinatorial phosphorylation code regulates AMPA receptor removal during distinct forms of synaptic plasticity

Synaptic plasticity is essential for memory encoding and stabilization of neural network activity. Plasticity is impaired in neurodegenerative conditions including Alzheimer disease (AD). A central factor in AD is amyloid precursor protein (APP). Previous studies have suggested APP involvement in synaptic plasticity, but physiological roles of APP are not well understood. Here, we identified combinatorial phosphorylation sites within APP that regulate AMPA receptor trafficking during different forms of synaptic plasticity. Dual phosphorylation sites at threonine-668/serine-675 of APP promoted endocytosis of the GluA2 subunit of AMPA receptors during homeostatic synaptic plasticity. APP was also required for GluA2 internalization during NMDA receptor-dependent long-term depression, albeit via a distinct pair of phosphoresidues at serine-655/threonine-686. These data implicate APP as a central gate for AMPA receptor internalization during distinct forms of plasticity, unlocked by specific combinations of phosphoresidues, and suggest that APP may serve broad functions in learning and memory.

Phosphorylation of tau protein based on the activity of kinases and phosphatases in various forms of synaptic plasticity.

The aim of this study is to show the relationship between the change in the strengthening of synaptic plasticity and tau phosphorylation and tau-kinases and phosphatase. The averages of the field excitatory-postsynaptic potential (fEPSP) and population spike (PS) in the last 5 min were used as a measure of LTP, LTD and MP. Total and phosphorylated levels of tau, kinases and phosphatases were evaluated by western blot and mRNA levels were evaluated by RT-qPCR. The stimulation of synapses by HFS and LFS+HFS increased the phosphorylation of total-tau and phospho-tau at the Thr181, Ser202/Thr205, Ser396 and Ser416 residues, and these were accompanied by increased enzymatic activity of Akt, ERK1/2. Theincreased phosphorylation of tau may mediate maintenance of LTP. If the increase in phosphorylation of tau cannot be prevented, together with inhibition of the subsequent LTP, this may indicate that the physiological role of hyperphosphorylated tau in synaptic plasticity may extend to pathological processes.

MEDICAL PHYSIOLOGY: ADVANCEMENTS IN TEACHING APPROACHES AT MEDICAL UNIVERSITIES

This article addresses the pressing issues of training modern medical and dental doctors as well as masters in biology at higher medical institutions, examining contemporary theoretical and practical approaches to integrating medical physiology as a fundamental medical amd biological discipline. It delves into current challenges in teaching physiology within the modern educational landscape, particularly focusing on the Department of Physiology at the Poltava State Medical University. This discipline is delivered by the Department of Physiology for students of the second (Master) level of higher education in the field "Healthcare" and "Biology". Physiology is a cornerstone discipline that fosters interdisciplinary integration in medical education, bridging theoretical knowledge with practical application in clinical settings. Emphasizing a practically oriented teaching principle, the article underscores the pivotal role of physiology in preparing students for clinical practice. The department adopts a comprehensive approach, developing and updating educational materials and manuals, including laboratory work with detailed descriptions of physiological research methods. Highlighting the department's achievements, it mentions their contribution to the first Ukrainian translation of the renowned physiology textbook "Medical Physiology” by Guyton and Hall in two volumes. It concludes by stressing the importance of enhancing the quality of education in medical institutions through continuous improvements in teaching practices, integration of advanced scientific developments and technologies, and the provision of modern educational resources and facilities, particularly in the field of physiology, which serves as the theoretical backbone of clinical medicine.

PRACTICAL APPROACH IN DELIVERING THEME "AUTONOMIC REFLEXES AND THEIR CLINICAL APPLICATION" AT THE DEPARTMENT OF PHYSIOLOGY, POLTEVE STATE MEDICAL UNIVERSITY

In the system of higher medical education, physiology is a fundamental discipline and occupies an important place in the system of training highly qualified medical specialists. In the system of higher medical education, physiology stands as a cornerstone discipline, holding a pivotal role in shaping the competencies of future medical professionals. The scientific and pedagogical staff at the Department of Physiology, Poltava State Medical University, is dedicated to nurturing students' capacity to analyze and synthesize both theoretical and practical knowledge, laying the groundwork for clinical acumen in future specialists. This article presents a hands-on approach to teaching the topic "Autonomic Reflexes and Their Clinical Applications" within the contemporary educational landscape, targeting second-year master's and first-year bachelor's students. Highlighting the practical significance of this topic in the future medical practice, it underscores how mastering autonomic reflexes equips students with the skills to influence internal organ activity and administer emergency medical care. Such an approach not only fosters student engagement with the subject matter but also cultivates a deeper appreciation for physiology as a whole. The article outlines the instructional principles, spanning from theoretical discourse to practical exercises, emphasizing the integral role of physiology in higher medical education. By advocating for the study of physiology as a foundational science, the article underscores its role in fostering interdisciplinary integration and shaping clinical reasoning—an essential aspect of quality medical training in today's educational landscape.

Biochemical and structural characterization reveals Rv3400 codes for β-phosphoglucomutase in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) adapt to various host environments and utilize a variety of sugars and lipids as carbon sources. Among these sugars, maltose and trehalose, also play crucial role in bacterial physiology and virulence. However, some key enzymes involved in trehalose and maltose metabolism in Mtb are not yet known. Here we structurally and functionally characterized a conserved hypothetical gene Rv3400. We determined the crystal structure of Rv3400 at 1.7 Å resolution. The crystal structure revealed that Rv3400 adopts Rossmann fold and shares high structural similarity with haloacid dehalogenase family of proteins. Our comparative structural analysis suggested that Rv3400 could perform either phosphatase or pyrophosphatase or β-phosphoglucomutase (β-PGM) activity. Using biochemical studies, we further confirmed that Rv3400 performs β-PGM activity and hence, Rv3400 encodes for β-PGM in Mtb. Our data also confirm that Mtb β-PGM is a metal dependent enzyme having broad specificity for divalent metal ions. β-PGM converts β-D-glucose-1-phosphate to β-D-glucose-6-phosphate which is required for the generation of ATP and NADPH through glycolysis and pentose phosphate pathway, respectively. Using site directed mutagenesis followed by biochemical studies, we show that two Asp residues in the highly conserved DxD motif, D29 and D31, are crucial for enzyme activity. While D29A, D31A, D29E, D31E and D29N mutants lost complete activity, D31N mutant retained about 30% activity. This study further helps in understanding the role of β-PGM in the physiology of Mtb.

Affinity Purification-Mass Spectrometry and Single Fiber Physiology/Proteomics Reveals Mechanistic Insights of C18ORF25.

C18ORF25 was recently shown to be phosphorylated at S67 by AMP-activated protein kinase (AMPK) in the skeletal muscle, following acute exercise in humans. Phosphorylation was shown to improve the ex vivo skeletal muscle contractile function in mice, but our understanding of the molecular mechanisms is incomplete. Here, we profiled the interactome of C18ORF25 in mouse myotubes using affinity purification coupled to mass spectrometry. This analysis included an investigation of AMPK-dependent and S67-dependent protein/protein interactions. Several nucleocytoplasmic and contractile-associated proteins were identified, which revealed a subset of GTPases that associate with C18ORF25 in an AMPK- and S67 phosphorylation-dependent manner. We confirmed that C18ORF25 is localized to the nucleus and the contractile apparatus in the skeletal muscle. Mice lacking C18Orf25 display defects in calcium handling specifically in fast-twitch muscle fibers. To investigate these mechanisms, we developed an integrated single fiber physiology and single fiber proteomic platform. The approach enabled a detailed assessment of various steps in the excitation-contraction pathway including SR calcium handling and force generation, followed by paired single fiber proteomic analysis. This enabled us to identify >700 protein/phenotype associations and 36 fiber-type specific differences, following loss of C18Orf25. Taken together, our data provide unique insights into the function of C18ORF25 and its role in skeletal muscle physiology.

ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.

The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the enzymatic activity of TMPRSS2 in a non-catalytic manner. Furthermore, we demonstrate that ACE2 knockdown inhibits TMPRSS2-mediated cleavage of IAV hemagglutinin (HA) in Calu-3 human airway cells and suppresses virus titers 100- to 1.000-fold. Transient expression of ACE2 in ACE2-deficient cells increased TMPRSS2-mediated HA cleavage and IAV replication. ACE2 knockdown also reduced titers of MERS-CoV and prevented S cleavage by TMPRSS2 in Calu-3 cells. By contrast, proteolytic activation and multicycle replication of IAV with multibasic HA cleavage site typically cleaved by furin were not affected by ACE2 knockdown. Co-immunoprecipitation analysis revealed that ACE2-TMPRSS2 interaction requires the enzymatic activity of TMPRSS2 and the carboxypeptidase domain of ACE2. Together, our data identify ACE2 as a new co-factor or stabilizer of TMPRSS2 activity and as a novel host cell factor involved in proteolytic activation and spread of IAV in human airway cells. Furthermore, our data indicate that ACE2 is involved in the TMPRSS2-catalyzed activation of additional respiratory viruses including MERS-CoV.IMPORTANCEProteolytic cleavage of viral envelope proteins by host cell proteases is essential for the infectivity of many viruses and relevant proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of several respiratory viruses, including influenza A virus. TMPRSS2 was previously shown to interact with angiotensin-converting enzyme 2 (ACE2). Here, we report the mechanistic details of this interaction. We demonstrate that ACE2 increases or stabilizes the enzymatic activity of TMPRSS2. Furthermore, we describe ACE2 involvement in TMPRSS2-catalyzed cleavage of the influenza A virus hemagglutinin and MERS-CoV spike protein in human airway cells. These findings expand our knowledge of the activation of respiratory viruses by TMPRSS2 and the host cell factors involved. In addition, our results could help to elucidate a physiological role for TMPRSS2.

Stochastic brain dynamics exhibits differential regional distribution and maturation-related changes

Functional magnetic resonance imaging (fMRI) is a powerful non-invasive method for studying brain function by analyzing blood oxygenation level-dependent (BOLD) signals. These signals arise from intricate interplays of deterministic and stochastic biological elements. Quantifying the stochastic part is challenging due to its reliance on assumptions about the deterministic segment. We present a methodological framework to estimate intrinsic stochastic brain dynamics in fMRI data without assuming deterministic dynamics. Our approach utilizes Approximate Entropy and its behavior in noisy series to identify and characterize dynamical noise in unobservable fMRI dynamics. Applied to extensive fMRI datasets (645 Cam-CAN, 1086 Human Connectome Project subjects), we explore lifelong maturation of intrinsic brain noise. Findings indicate 10% to 60% of fMRI signal power is due to intrinsic stochastic brain elements, varying by age. These components demonstrate a physiological role of neural noise which shows a distinct distributions across brain regions and increase linearly during maturation.

Atlas of cardiac endothelial cell enhancer elements linking the mineralocorticoid receptor to pathological gene expression.

Endothelial cells play crucial roles in physiology and are increasingly recognized as therapeutic targets in cardiovascular disease. Here, we analyzed the regulatory landscape of cardiac endothelial cells by assessing chromatin accessibility, histone modifications, and 3D chromatin organization and confirmed the functional relevance of enhancer-promoter interactions by CRISPRi-mediated enhancer silencing. We used this dataset to explore mechanisms of transcriptional regulation in cardiovascular disease and compared six different experimental models of heart failure, hypertension, or diabetes. Enhancers that regulate gene expression in diseased endothelial cells were enriched with binding sites for a distinct set of transcription factors, including the mineralocorticoid receptor (MR), a known drug target in heart failure and hypertension. For proof of concept, we applied endothelial cell-specific MR deletion in mice to confirm MR-dependent gene expression and predicted direct MR target genes. Overall, we have compiled here a comprehensive atlas of cardiac endothelial cell enhancer elements that provides insight into the role of transcription factors in cardiovascular disease.

Water-Soluble Coffee Melanoidins Inhibit Digestive Proteases.

Coffee is one of the most popular beverages around the world and its consumption contributes to the daily intake of dietary melanoidins. Despite the emerging physiological role of food melanoidins, their effect on digestive processes has not been studied so far. In this study, the activity of the gastrointestinal enzymes pepsin and trypsin was investigated in the presence of water-soluble coffee melanoidins. The gastric enzyme pepsin is only slightly affected, whereas the intestinal enzyme trypsin is severely inhibited by coffee melanoidins. The intestinal digestibility of casein was significantly inhibited by coffee melanoidins at a concentration achievable by regular coffee consumption. The inhibition of proteolytic enzymes by coffee melanoidins might decrease the nutritional value of dietary proteins.

Dual-Targeting Gold Nanoparticles: Simultaneous Decoration with Ligands for Co-Transporters SGLT-1 and B0AT1

Sodium–glucose co-transporter 1 (SGLT1) and sodium-dependent neutral amino acid transporter (B0AT1) are mainly expressed on the membrane of enterocytes, a type of epithelial cell found in the intestines. In addition to their physiological role in the absorption of nutrients, a protective role in the integrity of the intestinal barrier has been established. The natural ligands of SGLT1 (d-glucose) and of B0AT1 (l-glutamine) can trigger a protective anti-inflammatory effect on the intestinal epithelium. The literature suggests the activation of common intracellular pathways upon engagement of the two transporters, whose functional forms are composed of oligomers or clusters. Simultaneous activation of these two co-transporters could lead to a potential multitarget and synergistic anti-inflammatory effect. Therefore, nanoplatforms containing multiple copies of the ligands could represent chemical tools to study the potential simultaneous activation of the two co-transporters. For these reasons, in this study, a set of different gold nanoparticles decorated with derivatives of d-glucose and of l-glutamine were designed and prepared. In particular, the synthesis of suitable sulfur-ending functionalized ligand derivatives, including a C-glucoside derivative, their anchoring to gold nanoparticles and their physical–chemical characterization have been carried out. The obtained nanostructures could represent promising multifunctional platforms for further investigation of the existence of possible multitarget and synergistic effects toward the two co-transporters SGLT1 and B0AT1.

The dispensability of 14-3-3 proteins for the regulation of human cardiac sodium channel Nav1.5.

14-3-3 proteins are ubiquitous proteins that play a role in cardiac physiology (e.g., metabolism, development, and cell cycle). Furthermore, 14-3-3 proteins were proposed to regulate the electrical function of the heart by interacting with several cardiac ion channels, including the voltage-gated sodium channel Nav1.5. Given the many cardiac arrhythmias associated with Nav1.5 dysfunction, understanding its regulation by the protein partners is crucial. In this study, we aimed to investigate the role of 14-3-3 proteins in the regulation of the human cardiac sodium channel Nav1.5. Amongst the seven 14-3-3 isoforms, only 14-3-3η (encoded by YWHAH gene) weakly co-immunoprecipitated with Nav1.5 when heterologously co-expressed in tsA201 cells. Total and cell surface expression of Nav1.5 was however not modified by 14-3-3η overexpression or inhibition with difopein, and 14-3-3η did not affect physical interaction between Nav1.5 α-α subunits. The current-voltage relationship and the amplitude of Nav1.5-mediated sodium peak current density were also not changed. Our findings illustrate that the direct implication of 14-3-3 proteins in regulating Nav1.5 is not evident in a transformed human kidney cell line tsA201.

Redox Reactivity of Nonsymbiotic Phytoglobins towards Nitrite.

Nonsymbiotic phytoglobins (nsHbs) are a diverse superfamily of hemoproteins grouped into three different classes (1, 2, and 3) based on their sequences. Class 1 Hb are expressed under hypoxia, osmotic stress, and/or nitric oxide exposure, while class 2 Hb are induced by cold stress and cytokinins. Both are mainly six-coordinated. The deoxygenated forms of the class 1 and 2 nsHbs from A. thaliana (AtHb1 and AtHb2) are able to reduce nitrite to nitric oxide via a mechanism analogous to other known globins. NsHbs provide a viable pH-dependent pathway for NO generation during severe hypoxia via nitrite reductase-like activity with higher rate constants compared to mammalian globins. These high kinetic parameters, along with the relatively high concentrations of nitrite present during hypoxia, suggest that plant hemoglobins could indeed serve as anaerobic nitrite reductases in vivo. The third class of nsHb, also known as truncated hemoglobins, have a compact 2/2 structure and are pentacoordinated, and their exact physiological role remains mostly unknown. To date, no reports are available on the nitrite reductase activity of the truncated AtHb3. In the present work, three representative nsHbs of the plant model Arabidopsis thaliana are presented, and their nitrite reductase-like activity and involvement in nitrosative stress is discussed. The reaction kinetics and mechanism of nitrite reduction by nsHbs (deoxy and oxy form) at different pHs were studied by means of UV-Vis spectrophotometry, along with EPR spectroscopy. The reduction of nitrite requires an electron supply, and it is favored in acidic conditions. This reaction is critically affected by molecular oxygen, since oxyAtHb will catalyze nitric oxide deoxygenation. The process displays unique autocatalytic kinetics with metAtHb and nitrate as end-products for AtHb1 and AtHb2 but not for the truncated one, in contrast with mammalian globins.

Exploring the Intricacies of Pancreatic Duct Tributaries: Variations in Length, Angle of Entry, and Alternating Patterns in Human Cadavers by Dissection

Background: The pancreatic duct system plays a pivotal role in human physiology, facilitating the transport of digestive enzymes and secretions essential for gastrointestinal function. While anatomists have extensively investigated the pancreas's ductal network, the intricacies of pancreatic duct tributaries, including variations in length, angle of entry, and alternating patterns, have continued to captivate scientific inquiry. Aim: To find out the variations in length, angle of entry, and alternating patterns of pancreatic duct tributaries, and discuss the potential clinical implications of our discoveries. Materials and Methods: This study, conducted on 50 human cadavers (comprising 35 perinates and 15 adults), aimed to comprehensively explore the complexities of pancreatic duct tributaries through meticulous dissection. Results: Our research unveiled the following key findings: Variations in Length and Angle of Entry: We observed a remarkable diversity in the number and length of tributaries that join the main pancreatic duct. Additionally, the entry angle exhibited substantial variation, with right-angled tributaries prevalent in 70% of specimens and acute angles in 30%. Understanding these anatomical nuances is crucial for surgical procedures to mitigate inadvertent ductal injury. Alternating and Herringbone Patterns: In 98% of specimens, tributaries alternated between superior and inferior positions along the main pancreatic duct. This alternating pattern may influence the flow of pancreatic secretions and the pathogenesis of pancreatic diseases. In contrast, the rare Herringbone pattern was observed in only 2% of cases, highlighting the unique nature of this anatomical variant. Conclusion: This study contributes valuable insights into the intricate world of pancreatic duct tributaries. By elucidating their anatomy and characteristics, we enhance the safety and efficacy of clinical interventions and expand our understanding of pancreatic physiology and pathology. Further research may delve into the functional implications of these anatomical variations, paving the way for advancements in pancreatic healthcare. KEYWORDS: Pancreatic Duct Tributaries, Anatomical Variations, Pancreatic Surgery, Pancreatic Physiology, Dissection, Herring Bone Pattern, Gastrointestinal Function.

A Review on the Role and Function of Cinnabarinic Acid, a "Forgotten" Metabolite of the Kynurenine Pathway.

In the human body, the majority of tryptophan is metabolized through the kynurenine pathway. This consists of several metabolites collectively called the kynurenines and includes, among others, kynurenic acid, L-kynurenine, or quinolinic acid. The wealth of metabolites, as well as the associated molecular targets and biological pathways, bring about a situation wherein even a slight imbalance in the kynurenine levels, both in the periphery and central nervous system, have broad consequences regarding general health. Cinnabarinic acid (CA) is the least known trace kynurenine, and its physiological and pathological roles are not widely understood. Some studies, however, indicate that it might be neuroprotective. Information on its hepatoprotective properties have also emerged, although these are pioneering studies and need to be replicated. Therefore, in this review, I aim to present and critically discuss the current knowledge on CA and its role in physiological and pathological settings to guide future studies.