Pathological Conditions Research Articles

Value of autopsy in the modern age: Discrepancy between clinical and autopsy diagnoses

BACKGROUND Autopsy is a medical procedure that consists of the examination of the corpse to determine the cause of death and obtain information on pathological conditions or injuries. In recent years, there has been a reduction in hospital autopsies and an increase in forensic autopsies. AIM To evaluate the utility of autopsy in the modern age and the discrepancy between clinical and autopsy diagnoses. METHODS A retrospective observational study was conducted on the reports of all 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021. RESULTS Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology; pulmonary disease was the cause of death in 23% of cases; and there was a discrepancy between clinical and autopsy diagnosis in 55% of cases. Group B, 2010-2013, 119 cases: 52% male, 46% infants, 48% neonatology; pulmonary disease was the cause of death in 25% of cases; and there was a discrepancy between clinical and autopsy diagnosis in 56% of cases. Group C, 2014-2017, 168 cases: sex equality, 37% infants, 25% gynecology; pulmonary disease was the cause of death in 24% of cases; and there was a discrepancy between clinical and autopsy diagnosis in 58% of cases. Group D, 2018-2021, 184 cases: 56% male, 38% adult, 32% gynecology; pulmonary disease was the cause of death in 27% of cases; and there was a discrepancy between clinical and autopsy diagnosis in 58% of cases. CONCLUSION The study of hospital autopsies reveals a 56.75% discrepancy between clinical diagnosis and autopsy, highlighting the importance of autopsies, especially for fetal and neonatal diseases, which represent 59% of cases.

Autologous blood in the management of ocular surface disorders

Autologous blood therapy has emerged as a promising modality in managing ocular surface disorders. This review provides a comprehensive overview of the current literature regarding the use of autologous blood in ocular surface disorders, encompassing its physiological basis, clinical applications, techniques, challenges, and future perspectives. The ocular surface, comprising the cornea, conjunctiva, and tear film, plays a critical role in maintaining visual function, and its disruption can lead to various pathological conditions. With its rich composition of growth factors, cytokines, and other bioactive molecules, autologous blood offers therapeutic potential in promoting corneal wound healing, reducing inflammation, and improving tear film stability. Clinical studies have demonstrated the efficacy and safety of autologous blood therapy in diverse ocular surface disorders, including persistent epithelial defects, neurotrophic keratopathy, and dry eye disease. However, challenges such as variability in treatment response, adverse effects, and optimal patient selection remain areas of concern. Further research is needed to elucidate the underlying mechanisms of action, refine treatment protocols, and explore synergistic approaches with other therapeutic modalities. Despite these challenges, autologous blood therapy holds promise as a valuable adjunctive treatment option for ocular surface disorders, offering new avenues for improving patient outcomes and quality of life. This review examines the mechanisms underlying ocular surface disorders while discussing existing autologous blood-based therapies for managing these disorders. Current clinical trials are also summarized, and a comparison between autologous blood therapy and conventional eyedrops is attempted. Finally, safe techniques and protocols for autologous blood medicine are elucidated, and adverse effects and future perspectives of this novel therapy are reviewed.

Pseudomonas aeruginosa: A Bacterial Platform for Biopharmaceutical Production

Pseudomonas aeruginosa is a metabolically versatile opportunistic pathogen capable of surviving in a range of environments. The major contribution to these abilities relies on virulence factor production, e.g., exotoxins, phenazines, and rhamnolipids, regulated through a hierarchical system of communication, named quorum sensing (QS). QS involves the production, release, and recognition of two classes of diffusible signal molecules: N-acyl-homoserine lactones and alkyl-quinolones. These present a central role during P. aeruginosa infection, regulating bacterial virulence and the modulation of the host immune system. The influence of this arsenal of virulence factors on bacterial–host interaction makes P. aeruginosa a highly potential platform for the development of biopharmaceuticals. Here, we comprehensively reviewed the therapeutical applications of P. aeruginosa virulence factors and quorum sensing signaling molecules on pathological conditions, ranging from infections and inflammation to cancer disease.

FTO in health and disease

Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer. It also summarizes the established molecules with FTO-inhibiting activity. Given the extensive impact of FTO on both physiology and pathophysiology, this overview provides illustrative insights into its roles, rather than an exhaustive account. A proper understanding of FTO function in human diseases could lead to new treatment approaches, potentially unlocking novel avenues for addressing both metabolic disorders and malignancies. The evolving insights into FTO’s regulatory mechanisms hold great promise for future advancements in disease treatment and prevention.

Functional Neuroanatomy of the Normal and Pathological Basal Ganglia.

The term "basal ganglia" refers to a group of interconnected subcortical nuclei engaged in motor planning and movement initiation, executive functions, behaviors, and emotions. Dopamine released from the substantia nigra is the underlying driving force keeping the basal ganglia network under proper equilibrium and, indeed, reduction of dopamine levels triggers basal ganglia dysfunction, setting the groundwork for several movement disorders. The canonical basal ganglia model has been instrumental for most of our current understanding of the normal and pathological functioning of this subcortical network. This model explains how cortical information flows through the basal ganglia nuclei back to the cortex by going through two pathways with opposing effects that together lead to the proper execution of a given movement. The basal ganglia model has paved the way for the standard clinical management of Parkinson's disease, where pharmacological and neurosurgical treatments in place collectively afford an impressive symptomatic alleviation. Although much of the model has remained, the canonical model has been enriched with new arrivals gathered from evidence provided in the last three decades. Here, we sought to provide a comprehensive review of the basal ganglia network, with emphasis on structure, connectivity patterns, and basic operational principles, both in normal and pathological conditions.

New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probes

Advanced molecular probes are required to study the functional activity of the Kv1.2 potassium channel in normal and pathological conditions. To address this, a fully active Kv1.2 channel fused with fluorescent protein mKate2 (K-Kv1.2) was engineered that has high plasma membrane presentation due to the S371T substitution, and hongotoxin 1 (HgTx1) fused with eGFP at the C-terminus (HgTx-G) was produced. HgTx-G and HgTx1 N-terminally labeled with Atto488 fluorophore were shown to be fluorescent probes of Kv1.2 in cells with dissociation constants (Kd) of 120 and 80 pM, respectively. K-Kv1.2 and HgTx-G were used as components of an analytical system to study peptide blockers of the channel and helped to find out that Ce1 and Ce4 peptides from Centruroides elegans venom possess high affinity (Kd of 10 and 30 pM) and selectivity for Kv1.2. Using molecular docking and molecular modeling techniques, the complexes of Kv1.2 with HgTx1, Ce1, and Ce4 were modeled, and determinants of the high affinity binding were proposed. New fluorescent probes and selective blockers of Kv1.2 can be used to resolve Kv1.2-related challenges in neuroscience and neuropharmacology.

Predictive Value of Serum Lactate Levels for Mortality in Patients with Hepatitis B-Related Decompensated Cirrhosis: A Retrospective Analysis

Aims/Background Decompensated cirrhosis is characterized by the progression of cirrhosis from an asymptomatic state to elevated portal pressure and marked deterioration of liver function. This pathological condition progresses rapidly following onset, significantly raising the risk for mortality. The aim of this study is to explore the association between serum lactate concentrations and mortality rates in individuals with hepatitis B-induced decompensated cirrhosis and to evaluate its potential as a clinical prognostic indicator. Methods This retrospective analysis involved 200 individuals (134 men and 66 women) diagnosed with decompensated cirrhosis related to hepatitis B and hospitalized between March 2017 and May 2023. Out of these patients, 162 survived while 38 did not. Clinical information and laboratory results, including the Model for End-Stage Liver Disease (MELD) score, Child-Pugh score, and serum lactate levels, were collected. Logistic regression was applied to identify mortality risk factors from the patient sample and groups categorized according to gender. The predictive value of serum lactate levels for mortality was assessed using the area under the curve (AUC), i.e., receiver operating characteristic (ROC) curve. Results The surviving patient group showed significantly lowered MELD scores, Child-Pugh scores, and serum lactate levels compared to those who were deceased (p < 0.05). Multivariate analysis revealed that the MELD score, Child-Pugh score, and serum lactate levels were independent predictors of mortality in patients with decompensated hepatitis B cirrhosis, with odds ratios (OR) of 1.321, 1.432, and 49.082, respectively (p = 0.012, 0.028, and <0.001, respectively). Additionally, the OR for serum lactate levels was notably higher in female patients compared to male patients (46.824 vs. 30.451). Thus, the MELD score, Child-Pugh score, and serum lactate levels are effective predictors for mortality in cirrhosis patients (AUCs = 0.628, 0.675, and 0.809; p = 0.014, 0.001, and <0.001, respectively), with serum lactate levels showing the most excellent predictive efficacy profile (sensitivity 65.8% and specificity 97.5%). Additionally, the AUC value for serum lactate levels was lower in male patients (0.785) compared to female patients (0.875), indicating that changes in serum lactate levels were more sensitive in female patients. In summary, serum lactate concentration is a prognostic indicator of mortality in individuals with decompensated cirrhosis due to hepatitis B, exhibiting higher predictive significance in female patients. Conclusion Deceased patients with decompensated cirrhosis linked to hepatitis B exhibit markedly increased serum lactate levels. Thus, monitoring serum lactate levels offers an effective tool for predicting patient prognosis, exhibiting higher sensitivity for disease detection in female patients.

Human Health, Environmental Comfort and Well-Being. Part 1. Engineering and Design Resources of the Bioindustry on the Way to Safe Competition with the Resources of Natural Biocenoses and Health-Saving Systems

Everyone has the right to the highest attainable standard of health, and modern preventive, preventive and rehabilitative manipulations promote health and well-being. Thanks to a number of fundamental projects on the study of human health at various levels (genomic, proteomic, and metabolomic), and molecular mechanisms of the development of pathological conditions, there has been a great leap in the field of applied sectors of industrial biotechnology, including segments of the pharmaceutical and food industries, significantly replenished health-saving resources and improved the quality of life of the population. This article will review the advanced achievements of fundamental and applied research, as well as promising areas of the bioindustry.

The Role of Macronutrients and Gut Microbiota in Neuroinflammation Post-Traumatic Brain Injury: A Narrative Review

Traumatic brain injury (TBI) represents a multifaceted pathological condition resulting from external forces that disrupt neuronal integrity and function. This narrative review explores the intricate relationship between dietary macronutrients, gut microbiota (GM), and neuroinflammation in the TBI. We delineate the dual aspects of TBI: the immediate mechanical damage (primary injury) and the subsequent biological processes (secondary injury) that exacerbate neuronal damage. Dysregulation of the gut–brain axis emerges as a critical factor in the neuroinflammatory response, emphasizing the role of the GM in mediating immune responses. Recent evidence indicates that specific macronutrients, including lipids, proteins, and probiotics, can influence microbiota composition and in turn modulate neuroinflammation. Moreover, specialized dietary interventions may promote resilience against secondary insults and support neurological recovery post-TBI. This review aims to synthesize the current preclinical and clinical evidence on the potential of dietary strategies in mitigating neuroinflammatory pathways, suggesting that targeted nutrition and gut health optimization could serve as promising therapeutic modalities in TBI management.

Decoding FGF/FGFR Signaling: Insights into Biological Functions and Disease Relevance

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions. By complementing current knowledge and emerging research, this review aims to enhance the understanding of FGF-FGFR-mediated signaling and its implications for health and disease, which will be crucial for therapeutic development against FGF-related pathological conditions.

Wnt Signaling Inhibitors as Therapeutic Approach in Ischemic Heart Disease

Wnt (wingless-type MMTV integration site family) signaling is an evolutionary conserved system highly active during embryogenesis, but in adult hearts has low activities under normal conditions. It is essential for a variety of physiological processes including stem cell regeneration, proliferation, migration, cell polarity, and morphogenesis, thereby ensuring homeostasis and regeneration of cardiac tissue. Its dysregulation and excessive activation during pathological conditions leads to morphological and functional changes in the heart resulting in impaired myocardial regeneration under pathological conditions such as myocardial infarction, heart failure, and coronary artery disease. Several groups of Wnt inhibitors have demonstrated the ability to modulate the Wnt pathway and thereby significantly reduce fibrosis and improve cardiac function after myocardial ischemia. Their inhibitory effect can be realized at multiple levels, which include the inhibition of Wnt ligands, the inhibition of Frizzled receptors, the stabilization of the β-catenin destruction complex, and the disruption of nuclear β-catenin interactions. In this review, we overview the function of Wnt signaling in responses of cardiac cells to pathological conditions, especially ischemic heart disease, with an emphasis on the use of inhibitors of this signaling as a therapeutic approach. Finally, we summarize the current knowledge about the potential of the targeting of Wnt signaling in therapeutic applications.

Polymorphonuclear myeloid-derived suppressor cells regulates immune recovery during HIV infection through PD-L1 and TGF-β pathways

BackgroundAlthough MDSCs are widely recognized for their immunoinhibitory effects in pathological conditions, their function during HIV infection particularly within the mechanisms underlying incomplete immune recovery remains elusive.MethodsWe conducted a cross-sectional study in which 30 healthy controls and 62 HIV-1-infected subjects [31 immunological non-responders (INRs) and 31 immunological responders (IRs)] were selected. The proportion of MDSCs was determined in each category of participants. Using flow cytometry and real-time PCR, immune regulatory molecules (including PD-L1, ARG1, iNOS, IL-10, TGF-β, and IDO) that are relevant for MDSCs activity were quantified. Furthermore, we investigated the impact of the blockade of PD-L1 and TGF-β pathways on MDSCs and their effects on CD4+ T-cells using in vitro functional experiments.ResultsPMN-MDSCs are more abundant and are negatively correlated to CD4 counts in HIV-infected individuals. In addition, PMN-MDSCs suppress CD4+ T-cell proliferation and IFN-γ production in INRs. Furthermore, correlations were found between PD-L1 expression on PMN-MDSCs and PD-1+ CD4+ T-cells. TGF-β expression on PMN-MDSCs was likewise enhanced in INRs. Importantly, inhibiting both PD-L1 and TGF-β pathways had a synergistic impact on restoring CD4+ T-cell activity in vitro.ConclusionsPMN-MDSCs expansion inhibits CD4+ T-cell responses. We suggest that targeting PD-L1 and TGF-β pathways together may significantly improve immune recovery in INRs.

The aldose reductase inhibitors AT-001, AT-003 and AT-007 attenuate human keratinocyte senescence

Human skin plays an important role protecting the body from both extrinsic and intrinsic factors. Skin aging at cellular level, which is a consequence of accumulation of irreparable senescent keratinocytes is associated with chronological aging. However, cell senescence may occur independent of chronological aging and it may be accelerated by various pathological conditions. Recent studies have shown that oxidative stress driven keratinocyte senescence is linked to the rate limiting polyol pathway enzyme aldose reductase (AR). Here we investigated the role of three novel synthetic AR inhibitors (ARIs) AT-001, AT-003 and AT-007 in attenuating induced skin cell senescence, in primary normal human keratinocytes (NHK cells), using three different senescence inducing agents: high glucose (HG), hydrogen peroxide (H2O2) and mitomycin-c (MMC). To understand the efficacy of ARIs in reducing senescence, we have assessed markers of senescence, including SA-β-galactosidase activity, γ-H2AX foci, gene expression of CDKN1A, TP53 and SERPINE1, reactive oxygen species generation and senescence associated secretory phenotypes (SASP). Strikingly, all three ARIs significantly inhibited the assessed senescent markers, after senescence induction. Our data confirms the potential role of ARIs in reducing NHK cell senescence and paves the way for preclinical and clinical testing of these ARIs in attenuating cell aging and aging associated diseases.

CHI3L1 in Multiple Sclerosis—From Bench to Clinic

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is likely to play a role in the physiological development of the CNS. CHI3L1 is primarily produced by CNS macrophages, microglia, and activated astrocytes. The CHI3L1 expression pattern in MS lesions might support the important role of astrocytes in modulating inflammatory processes in this disease. The potential applications of CHI3L1 as a biomarker in MS are multifactorial. The measurement of CHI3L1 in body fluids might find its role in the early diagnosis of MS. In further stages, the monitoring of CHI3L1 levels might provide information on disease severity and progression, enabling a better adjustment of therapeutic strategies. Importantly, CHI3L1 might potentially serve as a marker of ongoing glial activation, reflecting the dynamic response of the CNS cells to the inflammatory processes in MS. Although preliminary findings have been promising, further research is needed to validate the utility of CHI3L1 measurements in the diagnosis and prediction of the progression of MS. Additionally, comparisons with other biomarkers might be useful in clinical practice.

Mitigating inflammation and fibrosis: the therapeutic potential of quercetin liposomes in COPD

IntroductionChronic obstructive pulmonary disease (COPD) is a disease with severe therapeutic obstacles and high worldwide death rate. COPD progresses predominantly through inflammatory response followed by fibrotic destruction. Quercetin (Que), recognized for its anti-inflammatory effects, presents significant promise as a therapeutic candidate for COPD therapy. However, poor water solubility and low bioavailability of Que hinder its further clinical application. Liposomes are renowned for their unique structure and function, which provided an efficient approach for the delivery of Que in various drug delivery systems. This study was aim to prepare a novel Que liposome (Que-lipo) and administrated via intratracheal (i.t.) with cigarette smoke induced COPD mice. The underlying therapeutic mechanisms against lung damage of Que-lipo were explored.MethodsQue-lipo were prepared based on thin film dispersion method and administrated via intratracheal administration. The cigarette smoke induced COPD mice were established and a comprehensive approach was employed to explore the inflammation, pulmonary function and histopathology of lung after i.t. administration of Que-lipo, including enzyme-linked immunosorbent assay, histopathology and immunohistochemistry, reverse transcription-quantitative polymerase chain reaction.Results and discussionQue-lipo not only improved the solubility and biocompatibility of Que but also demonstrated effective cellular uptake in vitro. The inflammation, pulmonary function and pathological condition of lung were improved after i.t. administration of Que-lipo. Que-lipo also regulated the expression of key apoptosis-associated proteins such as Bcl-2 and caspase-3/7, leading to significant inhibition of apoptotic activity in COPD. Furthermore, Que-lipo markedly enhanced its ability to alleviate lung inflammation and fibrosis symptoms by modulating inflammation-related factors and fibrosis signaling molecules. The potential mechanisms of Que-lipo in treating COPD were elucidated, including the suppression of the NLRP3/IL-1β inflammasome pathway and the TGF-β1-related fibrosis signaling pathway.

A framework to automatically detect near-falls using a wearable inertial measurement cluster

Accurate and automatic assessments of body segment kinematics via wearable sensors are essential to provide new insights into the complex interactions between active lifestyle and fall risk in various populations. To remotely assess near-falls due to balance disturbances in daily life, current approaches primarily rely on biased questionnaires, while contemporary data-driven research focuses on preliminary fall-related scenarios. Here, we worked on an automated framework based on accurate trunk kinematics, enabling the detection of near-fall scenarios during locomotion. Using a wearable inertial measurement cluster in conjunction with evaluation algorithms focusing on trunk angular acceleration, the proposed sensor-framework approach revealed accurate distinguishment of balance disturbances related to trips and slips, thereby minimising false detections during activities of daily living. An important factor contributing to the framework’s high sensitivity and specificity for automatic detection of near-falls was the consideration of the individual’s gait characteristics. Therefore, the sensor-framework presents an opportunity to substantially impact remote fall risk assessment in healthy and pathological conditions outside the laboratory.

Liquid–liquid phase separation in neurodegenerative diseases: An updated understanding

Liquid–liquid phase separation (LLPS), once understood merely as a physicochemical phenomenon, has emerged over the past decade as a critical player in life processes. LLPS provides a novel framework for understanding the structure, function, and spatiotemporal regulation of intracellular biomolecules. Through LLPS, biomolecules within cells can spontaneously assemble into membraneless compartments, which allow precise regulation of biochemical reactions and influence critical cellular processes such as signal transduction and gene expression. Despite its recognized significance in basic biological research, the role of LLPS in human disease is still an area worthy of continued exploration. Currently, the most studied disorders in relation to LLPS are neurodegenerative diseases and cancer. In neurodegenerative diseases, LLPS is closely linked to protein misfolding and aggregation, processes that can lead to the formation of toxic assemblies, ultimately causing neuronal damage and death. In cancer, aberrant LLPS may contribute to the dysregulation of signaling pathways, promoting uncontrolled cell proliferation and metastasis. This review highlights recent advances regarding the role of LLPS in the pathogenesis of neurodegenerative diseases, discussing its function in these pathological conditions and proposing directions for future research. As research progresses, the potential role of LLPS in other human diseases will likely be uncovered, offering new avenues for diagnosis and therapy. Therefore, further investigation into the mechanisms of LLPS and its involvement in disease pathology will be crucial for advancing our understanding of human health and disease.

The Roles of Dietary Organic Trace Minerals on Animal Antioxidative Status, Gut Health, and Environmental Sustainability: A Review

The livestock industry is currently focused on improving production through sustainable nutrition practices. This has spurred scientists to investigate the potential of functional nutrients in providing health benefits beyond their nutritional value. The use of inorganic trace minerals (ITMs) has registered some successes but with some drawbacks arising from their low absorption rate, causing the excretion of copious amounts of trace minerals in manure, which pollutes the environment and becomes detrimental to soil physiology and crop health. Organic trace minerals (OTMs) are relatively more effective due to their stability and lower reactivity, although their functionality and pH depend on production processes. Here, we underscore the effects of OTM supplementation in animal diets to enhance the host’s antioxidant capacity and gut health and promote environmental sustainability, as presented in the graphical abstract. Through adequate dietary OTM supplementation, animals can develop powerful resistance against the negative effects of physiological stressors or diseases by reinforcing the host’s systemic antioxidant defenses and alleviating compromises on the gut’s structure and functions, the gut being the primary site of nutrient digestion and absorption. The high cost of OTMs and the inconsistent outcomes of some across different animal species present significant limitations. Therefore, further research is needed to determine species-specific OTM requirements to optimize health and performance without over-supplementation. Also, researchers should further investigate the impact of OTMs, alone or in combination with other functional nutrients on animals’ immunological responses during oxidative or pathological conditions.

Cribra orbitalia and Porotic hyperostosis on bone remains of the Bronze Age population from the Lower Volga region (search for the proliferation causes)

This study is devoted to defining the occurrence frequency of Cribra orbitalia and Porotic hyperostosis signs based on the data obtained and establishing the reasons for the spread of these pathological conditions in the study groups. The material for the study is series dating back to the Early, Middle and Late Bronze Ages from the Lower Volga region kurgan mounds. When analyzing bone remains, the occurrence of porotic hyperostosis on the skull and cribra orbitalia was taken into account. To identify significantly significant differences in the incidence of pathological abnormalities, the groups were compared using non-parametric mathematical criteria. Statistical calculations were carried out in the StatSoft, Inc. shell. (2011) STATISTICA. As a result of the study, it was estab-lished that the factors influencing the occurrence of signs of hemolytic diseases in the study group could be en-demic malaria, helminths, as well as nutritional stress caused by systematic starvation, lack of vitamin C, folic acid, cobalamin and iron.

The biliary ecosystem: a holistic perspective on critical scientific issues regarding biliary tract surgeries and diseases

The establishment of modern biliary surgery system, alongside pivotal scientific paradigm shifts, has heralded a new era featured by precision, personalization, life-cycle care, and multidisciplinary management in the treatment of both benign and malignant biliary diseases. However, two formidable challenges persist in haunting the treatment of biliary diseases: (1) The refinement of surgical techniques has reached a plateau in reducing the disability associated with benign biliary conditions and in improving survival outcomes in biliary tract cancers; (2) Traditional evidence-based clinical studies have shown limited power in addressing complex dilemmas, such as determining whether to excise or preserve pathological gallbladders or selecting the optimal biliary drainage strategy. Consequently, the authors propose the conceptual framework of "biliary ecosystem". In this model, diverse and abundant cholangiocytes represent forest, while blood vessels, nerves, and lymphatic vessels serve as nurturing soil, biliary stem cells function as seeds, bile flows like river network, and hepatocytes mark the river's origins. Both benign and malignant biliary diseases exhibit significant spatiotemporal dynamics. The bile ducts form the "macro" environment, bile constitutes the "sub-macro" environment, and diverse cellular niches create the microenvironment. Specific pathological biliary conditions are shaped by intricate regulatory mechanisms that operate across these three tiers. Within the biliary ecosystem, cellular subpopulations exist remarkable diversity with states of homeostasis, oscillation, perturbation, or imbalance, underpinned by complex signaling networks. This holistic approach allows us to reframe and critically examine the pressing scientific issues confronting biliary tract diseases. Based on this framework, the authors distill key scientific questions and offer preliminary recommendations for embracing the paradigm shift. The authors anticipate that this conceptual model will promote interdisciplinary integration and accelerate clinical and translational researches.