Pathogenetic Mechanisms Research Articles

The Intricate Relationship Between Pulmonary Fibrosis and Thrombotic Pathology: A Narrative Review

Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk–benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.

Neuroinflammation as an Integral Component of Neurodegeneration in Parkinson's Disease

Parkinson's disease (PD) is a progressively advancing neurodegenerative disorder, the pathogenetic mechanisms of which remain poorly understood. The disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. Given the improvement in the quality of medical care provided to the population, it is projected that the total number of patients diagnosed with PD worldwide will rise to 8.7 million by 2030. This review addresses the fundamental aspects of neuroinflammation in the context of PD pathogenesis. There is no doubt that pro-inflammatory immunological mechanisms play a critical role in the onset and progression of the disease. Neuronal-derived cells, such as microglia and astrocytes, act as inducers of neuroinflammation, affecting the permeability of the blood-brain barrier to peripheral immune-competent cells. Furthermore, cytokine patterns of the immune response in PD appear to exist. Potential therapeutic approaches for mitigating neuroinflammation in PD, which have been studied in experimental and in vitro models, are also discussed.

Manual medical technologies in complex treatment and rehabilitation of patients with primary osteoarthritis (literature review)

The review discusses the pathogenetic mechanisms of primary osteoarthritis (OA) formation. The recommendations of the Association of Rheumatologists of Russia on the main principles of rehabilitation for OA are presented, including drug and non-drug methods of pain syndrome correction, improvement of motor activity and quality of life of patients. Particular attention is paid to the mechanisms of osteopathic correction for OA, which are aimed at restoring the impaired biomechanics of the patient’s body, eliminating persistent muscle hypertonicity, peripheral sensitization, and aimed at regulating antinociceptive mechanisms. An important advantage of manual treatment is the possibility of its use before, during or after other types of treatment and the ability to enhance their therapeutic potential.

Inflammation as a link between depression and metabolic syndrome

Depression makes a major contribution to the overall global burden of disease, including the increased risk of a wide range of concomitant somatic pathology. А high percentage of mortality in psychiatric patients is attributed to physical diseases, mainly cardiovascular (CVD). Metabolic syndrome (MetS) is one of the risk factors for both the CVD and a frequent comorbid depression. The purpose of this review is to systematize data on the relationship between MetS and depression, in particular, on the shared pathogenetic mechanisms as systemic inflammation. The manuscript evaluates the issue of the use of hematological indices of systemic inflammation (HISIs) in the diagnosis of both MetS and affective pathology, and also provides data on new combined indicators, including the cellular link and lipidogram parameters. The latter include the ratios of lymphocytes and high-density lipoproteins (HDL) (Lymphocyte To High-Density Lipoprotein Ratio, LHR), neutrophils/HDL (Neutrophil To High-Density Lipoprotein Ratio, NHR), platelets/HDL (Platelet To High-Density Lipoprotein Ratio, PHR) and monocytes/HDL (Monocyte To High Density Lipoprotein Ratio, MHR). Understanding the relationship between hematological indices and metabolic syndrome in patients with depression can help identify individuals at high risk and identify timely preventive measures. Various clinical trials and studies indicate a link between hematological parameters and metabolic syndrome, but the question of choosing the most effective coefficients remains open. Further study of the problem can help identify potential risks of comorbid disorders and perform adequate preventive strategies.

Взаимосвязь миокинов и саркопенического ожирения с неалкогольной жировой болезнью печени при конституционально-экзогенном ожирении у детей

Obesity in children is associated with high risk for development and progression of nonalcoholic fatty liver disease (NAFLD). NAFLD has common pathogenetic mechanisms with sarcopenic obesity (SO), in the development of which such myokines as fibroblast growth factor 21 (FGF-21) and irisin play an important role. The study of their secretion peculiarities is relevant to the prospects of using myokines as diagnostic markers or indicators for drug therapy and physical activity control as well as in the development of target therapy for NAFLD. The connection between NAFLD and SO and changes in myokine profile in children is an understudied issue. The purpose of this research was to determine differences between groups of pediatric patients with the presence v. those with the absence of NAFLD in constitutional-exogenous obesity in myokine and SO levels. Methods used: a single-stage comparative single-center uncontrolled study of 95 children aged 12 to 18 y/o with constitutional-exogenous obesity: body mass index (BMI) standard deviation score (SDS)≥+2.0. Results: NAFLD was detected in 48% (n=50/95) [95% CI (42; 63)] of whom steatohepatitis was detected in 40% (n=20/50) [95% CI (26; 55)]. SO was detected in 96% (n=48/50) [95% CI (86; 99)] with NAFLD including children with steatohepatitis (n=20). The combination of SO with elevated FRF-21 levels and decreased irisin was associated with NAFLD (AUC=0.761, [95% CI (0.65; 0.87)]). The SO frequency was statistically significantly higher in NAFLD than in the SO absence (p<0.001). The predictive ability of the SO presence in relation to the detection of NAFLD was found to be high (PCPR=96%, [95% CI (88; 99)]). FRF-21 values above 60 pg/mL (AUC=0.689, [95% CI (0.57; 0.81)]) and irisin values below 7.86 μg/mL (AUC=0.703, 95% CI (0.58; 0.82)]) were associated with the presence of NAFLD. When comparing operational characteristics, no differences were found for AUC value while the best performance was demonstrated by regression model and cut-off point of irisin equal to 7.86 μg/mL. Conclusion: SO combined with changes in myokine profile is associated with NAFLD. Identification of the main factors influencing the NAFLD development in childhood is crucial in preventing the progression of liver damage.

Research progress on the cognitive deficit of Down syndrome patients

As the most common chromosomal disorder compatible to life, Down syndrome (DS) is caused by an extra copy of chromosome 21. Almost all DS patients have cognitive dysfunction. Therefore, it is important to study the underlying pathogenetic mechanism to elucidate its molecular basis. This article has provided a review for the molecular mechanisms of NRIP1 and DYRK1A genes, which have been closely associated with the cognitive dysfunctions of DS patients. It has also summarized the research progress on the mechanism of DS and development of new therapeutic strategies based on such studies, with an aim to provide insights into the prevention and treatment for the cognitive dysfunctions in DS patients.

Live Cell Imaging of Human Liver Fibrosis using Hepatic Micro-Organoids.

Due to the limitations of available in vitro systems and animal models, we lack a detailed understanding of the pathogenetic mechanisms and have minimal treatment options for liver fibrosis. Therefore, we engineered a live cell imaging system that assesses fibrosis in a human multi-lineage hepatic organoid in a microwell (i.e., microHOs). Transcriptomic analysis revealed that TGFβ1 converted mesenchymal cells in microHOs into myofibroblast-like cells resembling those in fibrotic human liver tissue. When pro-fibrotic intracellular signaling pathways were examined, the anti-fibrotic effect of receptor-specific tyrosine kinase inhibitors was limited to the fibrosis induced by the corresponding growth factor, which indicates their anti-fibrotic efficacy would be limited to fibrotic diseases solely mediated by that growth factor. Based upon transcriptomic and transcription factor activation analyses in microHOs, GSK3β and p38 MAPK inhibitors were identified as potential new broad-spectrum therapies for liver fibrosis. Other new therapies could subsequently be identified using the microHO system.

Pemphigus and Bullous Pemphigoid Following COVID-19 Vaccination: A Systematic Review

The COVID-19 pandemic has encouraged the rapid development and licensing of vaccines against SARS-CoV-2. Currently, numerous vaccines are available on a global scale and are based on different mechanisms of action, including mRNA technology, viral vectors, inactive viruses, and subunit particles. Mass vaccination conducted worldwide has highlighted the potential development of side effects, including ones with skin involvement. This review synthesizes data from 62 manuscripts, reporting a total of 142 cases of autoimmune blistering skin diseases (AIBDs) following COVID-19 vaccination, comprising 59 cases of pemphigus and 83 cases of bullous pemphigoid. Among the 83 bullous pemphigoid cases, 78 were BP, with additional cases including 2 oral mucous membrane pemphigoid, 1 pemphigoid gestationis, 1 anti-p200 BP, and 1 dyshidrosiform BP. The mean age of affected individuals was 72 ± 12.7 years, with an average symptom onset of 11 ± 10.8 days post-vaccination. Notably, 59% of cases followed vaccination with BNT162b2 (Pfizer-BioNTech), 51.8% were new diagnoses, and 45.8% occurred after the second dose. The purpose of our review is to analyze the cases of pemphigus and bullous pemphigoid associated with COVID-19 vaccination and to investigate the pathogenetic mechanisms underlying the new development or flare-up of these diseases in association with vaccination. Our results show that the association between COVID-19 vaccines and AIBDs is a possible event.

Efficiency of complex topical therapy and broadband pulsed non-coherent light in the treatment of erythematotelangiectatic subtype of rosacea

Rosacea is a chronic inflammatory dermatosis of facial localization. Treatment tactics for patients with rosacea is a complex task, since it depends on the severity and individual characteristics of the patient. Numerous studies determine the relevance of this problem. Observation of 22 patients, 11 of whom received only topical treatment with the erythematotelangiectatic subtype of rosacea treatment in the form of 15% azelaic acid, 0.5 % brimonidine tartrate gel, and 1 % metronidazole cream. In 11 other patients, topical treatment was combined with phototherapy – broadband incoherent pulsed light at intervals of 1 time in 4 weeks, 3 procedures per course. Evaluation of the effectiveness of therapy was carried out using the Antera 3D visualization and skin diagnostics device. Also, the dermatological index GSS (Global Severity Score) and the dermatological index of symptom scale (DISS) were used as clinical evaluation methods. The combination of 15 % azelaic acid, 0.5 % brimonidine tartrate gel, with broadband pulse therapy (3 procedures) showed higher efficiency than monotherapy with topical agents. The obtained results, indicating higher efficiency of the combined treatment method, can be explained by the synergistic effect of the combination of the physiotherapeutic factor and external drugs affecting the pathogenetic mechanisms of disease development.

Regulation of ovarian function in obese women: pathogenetic mechanisms

Considering the universally high rates of obesity among the population, including women of reproductive age, and the negative impact of obesity on female fertility, the interest in this problem in the modern world becomes understandable. Many researchers have confirmed the pattern of ovulatory dysfunction development because of metabolic disorders in obese women. The exact mechanism for the development of anovulation and infertility in women with obesity has not been established, however, many pathogenetic factors that affect reproductive function are already known. Obese women have a high risk of developing ovulatory dysfunction due to insulin resistance, hyperandrogenism, as well as subclinical inflammation, lipotoxicity, and disruption of adipokines due to excess adipose tissue, which generally leads to impaired steroidogenesis and regulation in the hypothalamic – pituitary – gonadal axis. Due to the high prevalence of obesity in women of reproductive age, the objective of this review was to examine the pathogenetic mechanisms of the impact of obesity on female fertility, as well as the impact of high body mass index on the results of assisted reproductive technology (ART) cycles. We carried out a literature search in the PubMed database for the entire period of publications using phrases such as “ovarian function + obesity,” “pathogenesis of ovarian dysfunction in obesity,” “ART + obesity,” and “perinatal outcomes + bariatric surgery”. The most relevant studies being selected, with domestic and foreign clinical recommendations used in preparing the manuscript.

PATHOGENETIC MECHANISMS OF PAPILLEDEMA DEVELOPMENT ON PREECLAMPSIA

Preeclampsia is a multisystem disease that can include cardiovascular changes, hematological disorders, liver and kidney failure, cerebral and visual symptoms. Currently, the presence of papilledema in preeclampsia characterizes the disease as severe. However, it is likely that the presence of papilledema does not always characterize vasogenic cerebral edema with increased intracranial pressure. The formation of blurred borders and papilledema may also be associated with impaired autoregulation in the head of the optic disc due to increased blood pressure and the presence of endothelial dysfunction in preeclampsia. It is also important to differentiate the true papilledema from the pseudopapilledema. The study carried out a detailed systematic analysis of modern domestic and foreign literature, devoted to the pathogenetic mechanisms of papilledema development in preeclampsia. The study used such information databases as: eLibrary, PubMed, Scopus, Cochrane Library, MEDLINE for the period from 2015 to May 2024. This literature review presents possible pathogenetic mechanisms of the development of papilledema against on preeclampsia, as well as modern approaches to the differential diagnosis of papilledema from pseudopapilledema. Further study of the pathogenetic mechanisms of papilledema development in hypertensive pregnancy disorders is necessary to identify high-risk patients and optimize their management and treatment tactics.

Studying the impact of probiotic agents on the pathogenetic and clinical features of generalized periodontitis

Generalized periodontitis remains one of the most prevalent dental diseases, complications of which significantly deteriorate patients’ quality of life. Currently, the use of probiotic agents is considered a promising direction to enhance the effectiveness of non-surgical treatment of this pathology. Studying the impact of different probiotics on the pathogenetic and clinical features of generalized periodontitis will allow proposing optimized protocols for comprehensive treatment, reducing patient rehabilitation periods and improving the overall dental health of the population. The aim of this study is to examine the influence of various probiotic agents on the pathogenetic and clinical characteristics, treatment effectiveness of generalized periodontitis in adult patients by analyzing professional scientific literature. The literature review provides a brief overview of various probiotic groups and discusses pathogenetic mechanisms of their interaction with the microbiota of oral biofilms. The immunomodulatory mechanisms of probiotics on local and systemic immune responses in patients with generalized periodontitis, inhibition of enzymes responsible for bone tissue resorption, are presented. The analysis results of scientific sources regarding the dynamics of changes in clinical symptoms, microbiological, immunological, and biochemical parameters of saliva and blood serum in individuals with generalized periodontitis receiving comprehensive rehabilitation using probiotic agents compared to patients treated with traditional protocols are provided. The study highlights statistical differences in clinical and laboratory indicators of periodontitis progression at different treatment intervals. Conclusions. The use of probiotic agents for treating patients with generalized periodontitis significantly influences the clinical course of the disease by altering the species composition of dental biofilms and modulating local immune and inflammatory reactions. However, the known results of experimental and clinical studies often have conflicting findings regarding the efficacy of specific probiotic strains and the duration of inflammatory process stabilization over extended periods after treatment, which means a further study is required.

Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy.

Osteoarthritis (OA) is a chronic, degenerative joint disease primarily characterised by damage to the articular cartilage, synovitis and persistent pain, and has become one of the most common diseases worldwide. In OA cartilage, various forms of cell death have been identified, including apoptosis, necroptosis and autophagic cell death. Ever-growing observations indicate that ferroptosis, a newly-discovered iron-dependent form of regulated cell death, is detrimental to OA occurrence and progression. In this review, we first analyse the pathogenetic mechanisms of OA by which iron overload, inflammatory response and mechanical stress contribute to ferroptosis. We then discuss how ferroptosis exacerbates OA progression, focusing on its impact on chondrocyte viability, synoviocyte populations and extracellular matrix integrity. Finally, we highlight several potential therapeutic strategies targeting ferroptosis that could be explored for the treatment of OA.

Posttraumatic stress disorder and metabolic syndrome: the role of some biofactors in treatment

Post-traumatic stress disorder (PTSD) and metabolic syndrome (MetS) are often comorbidities and share neurobiological and clinical features. In particular, the results of meta-analyses indicate a higher prevalence of MetS in patients with PTSD compared to the general population. At the same time, PTSD is also a known risk factor for MetS. The involvement of common pathogenetic mechanisms characteristic of both conditions partially explains this coincidence. Insufficient intake and deficiency of certain biofactors, especially micronutrients (vitamins and essential minerals), are associated with an increased risk of MetS, type 2 diabetes mellitus, and cardiovascular diseases, and maintaining their physiological content in the body reduces this risk. Taking nutritional supplements with certain biofactors may help as an adjunct to conventional therapy to prevent and treat PTSD and, more often than not, MetS at the same time. This is because both conditions are linked to deficiencies in a number of biofactors. This review aims to discuss the role of several biofactors, including α-lipoic acid, vitamin B1/benfotiamine, L-carnitine and acetyl-L-carnitine, ω-3 polyunsaturated fatty acids, quercetin, magnesium, vitamins D and E, polyphenols, in the prevention and treatment of PTSD and MetS comorbidity, as well as to analyze new trends and future research directions. We conducted the search in databases such as Scopus, Science Direct (from Elsevier), PubMed, and MEDLINE. The keywords used were “post-traumatic stress disorder”, “metabolic syndrome”, and “biofactors”. We manually searched the bibliography of publications to identify research results that were not found during the online search.

Postprandial hypoglycaemia after gastric bypass in type 2 diabetes: pathophysiological mechanisms and clinical implications.

Postprandial hypoglycaemia (PPHG) is a frequent late complication of Roux-en-Y gastric bypass (RYGB) in people without diabetes. We aimed to examine the pathogenetic mechanisms of PPHG and its clinical consequences in people with a history of type 2 diabetes. In this case-control study, 24 participants with type 2 diabetes treated with RYGB (14 women; median [IQR] age 53.5 [13.8] years, BMI 29.3 [6.3] kg/m2, HbA1c 36.0 [6.2] mmol/mol [5.4% (0.6%)]) underwent a dual-tracer, frequently sampled, 300 min, 75 g OGTT for the diagnosis of PPHG (glucose nadir <3.0 mmol/l, or <3.3 mmol/l with symptoms). Plasma glucose, glucose tracers, insulin, C-peptide, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, adrenaline (epinephrine), noradrenaline (norepinephrine), cortisol and NEFAs were measured. Mathematical models were implemented to estimate glucose metabolic fluxes and beta cell function. ECG recordings, cognitive testing and hypoglycaemia awareness assessments were repeated during the OGTT. Glycaemic levels and dietary habits were assessed under free-living conditions. PPHG occurred in 12 (50%) participants, mostly without symptoms, due to excessive tracer-derived glucose clearance (mean group difference ± SE in AUC0-180 min +261±72 ml min-1 kg-1 × min) driven by higher whole-body insulin sensitivity and early glucose-stimulated hyperinsulinaemia, the latter depending on lower insulin clearance and enhanced beta cell function, regardless of incretin hormones. PPHG participants also had defective counterregulatory hormone responses to hypoglycaemia, preventing a physiological increase in endogenous glucose production and the appearance of symptoms and signs of sympathetic cardiovascular activation and neuroglycopenia. PPHG was associated with more frequent and prolonged hypoglycaemia on 14 day continuous glucose monitoring and alterations in free-living dietary habits. Our results demonstrate that post-bypass PPHG occurs frequently in individuals with a history of type 2 diabetes, often without warning symptoms, and expose its complex pathogenetic mechanisms, revealing potential therapeutic targets.

A clinical case of spontaneous coronary artery dissection in a young patient

Аim. To describe a clinical case of acute myocardial infarction in a young patient caused by spontaneous dissection of the coronary artery.Material and methods. The patient, a 32-year-old man, was hospitalized in the cardiology department with a clinical picture of acute coronary syndrome. When collecting anamnestic data, it was established that the patient has an aggravated cardiovascular, hereditary, pharmacological anamnesis and concomitant pathology. A special attitude of the patient to hisdisease in the form of an anosognosic reaction was revealed. The data of the coronary angiography study determined further tactics of patient management at the inpatient stage.Results. Taking into account the clinical picture, the dynamics of electrocardiograms, the results of laboratory diagnostics, acute myocardial infarction with ST segment elevation on the electrocardiogram was preliminarily diagnosed. During coronary angiography, spontaneous coronary artery dissection was detected in the patient, which was the main cause of acute left ventricular myocardial infarction. A decision was made to implant 3 stents in order to completely cover the dissection zone of the anterior interventricular branch of the left coronary artery. The choice of conservative and/or surgical tactics for managing patients with spontaneous coronary artery dissection is debatable. After percutaneous coronary intervention, drug therapy was prescribed, including dual antiplatelet therapy. The patient noted an improvement in his well-being, without relapses of pain syndrome. In the dynamics of inpatient treatment, according to echocardiographic examination, an aneurysm of the apex of the left ventricle with a mural thrombus was detected, which required correction of drug therapy, taking into account the increased risks of thromboembolic and hemorrhagic complications.Conclusion. This clinical case demonstrates that spontaneous dissection of the coronary artery is one of the pathogenetic mechanisms of the formation of the clinical picture of acute coronary syndrome and affects the development of complications and further prognosis.

The Role of Trace Elements in COPD: Pathogenetic Mechanisms and Therapeutic Potential of Zinc, Iron, Magnesium, Selenium, Manganese, Copper, and Calcium.

Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory airway disorder characterized by a gradual decline in lung function and increased oxidative stress. Both oxidative stress and inflammation are central to its pathophysiology, with trace elements such as zinc, copper, iron, manganese, magnesium, selenium, and calcium playing key roles in various cellular processes. This article reviews the role of trace elements in COPD, focusing on their involvement in disease pathogenesis and their therapeutic potential. Specifically, we examine the effects of zinc, copper, iron, magnesium, manganese, selenium, and calcium in COPD. We performed a comprehensive narrative review of the literature across databases including PubMed, Web of Science, Cochrane Library, and Google Scholar, identifying studies that explore the therapeutic effects of trace elements in COPD. The studies included in the review consisted of cohort analyses, randomized controlled trials, and clinical investigations. Zinc, copper, iron, magnesium, manganese, selenium, and calcium are critical to both the pathophysiology and management of COPD. These trace elements contribute to the regulation of inflammation, the modulation of oxidative stress, and the maintenance of lung function. Zinc and copper, for instance, reduce oxidative stress and modulate immune responses, while iron is essential for oxygen transport. Magnesium, manganese, selenium, and calcium are vital for muscle function, respiratory performance, reducing inflammation, and improving pulmonary function. The minerals zinc, copper, iron, magnesium, manganese, selenium, and calcium may contribute to beneficial effects as part of the standard therapeutic management of COPD. Maintaining optimal levels of these trace elements may support the regulation of inflammatory processes, a reduction in oxidative stress, and an improvement in the pulmonary function. However, further clinical research is necessary to confirm their efficacy and establish safe dosage recommendations in COPD treatment.

Constitutive opening of the Kv7.2 pore activation gate causes KCNQ2-developmental encephalopathy

Pathogenic variants in KCNQ2 encoding Kv7.2 voltage-gated potassium channel subunits cause developmental encephalopathies (KCNQ2-encephalopathies), both with and without epilepsy. We herein describe the clinical, in vitro, and in silico features of two encephalopathy-causing variants (A317T, L318V) in Kv7.2 affecting two consecutive residues in the S6 activation gate that undergoes large structural rearrangements during pore opening; the disease-causing A356T variant in KCNQ3, paralogous to the A317T variant in KCNQ2, was also investigated. Currents through KCNQ2 mutant channels displayed increased density, hyperpolarizing shifts in activation gating, faster activation and slower deactivation kinetics, and resistance to changes in the cellular concentrations of phosphatidylinositol 4,5-bisphosphate (PIP2), a critical regulator of Kv7 channel function; all these features are consistent with a strong gain-of-function effect. An increase in the probability of single-channel opening, with no change in membrane abundance or single-channel conductance, was responsible for the observed gain-of-function effects. All-atom molecular dynamics simulations revealed that the mutations widened the inner pore gate and stabilized a constitutively open channel configuration in the closed state, with minimal effects on the open conformation. Thus, mutation-induced stabilization of the inner pore gate open configuration is a molecular pathogenetic mechanism for KCNQ2-related encephalopathies.

Emerging roles of mechanosensitive ion channels in ventilator induced lung injury: a systematic review.

The pathogenetic mechanisms of ventilator-induced lung injury (VILI) still need to be elucidated. The mechanical forces during mechanical ventilation are continually sensed and transmitted by mechanosensitive ion channels (MSICs) in pulmonary endothelial, epithelial, and immune cells. In recent years, MSICs have been shown to be involved in VILI. A systematic search across PubMed, the Cochrane Library, Web of Science, and ScienceDirect was performed from inception to March 2024, and the review was conducted in accordance with PRISMA guidelines. The potential eligible studies were evaluated by two authors independently. Study characteristics, quality assessment, and potential mechanisms were analyzed. We included 23 eligible studies, most of which were performed with murine animals in vivo. At the in vitro level, 52% and 48% of the experiments were conducted with human or animal cells, respectively. No clinical studies were found. The most reported MSICs include Piezo channels, transient receptor potential channels, potassium channels, and stretch-activated sodium channels. Piezo1 has been the most concerned channel in the recent five years. This study found that signal pathways, such as RhoA/ROCK1, could be enhanced by cyclic stretch-activated MSICs, which contribute to VILI through dysregulated inflammation and immune responses mediated by ion transport. The review indicates the emerging role of MSICs in the pathogenesis of VILI, especially as a signal-transmitting link between mechanical stretch and pathogenesis such as inflammation, disruption of cell junctions, and edema formation. Mechanical stretch stimulates MSICs to increase transcellular ion exchange and subsequently generates VILI through inflammation and other pathogeneses mediated by MSICs signal-transmitting pathways. These findings make it possible to identify potential therapeutic targets for the prevention of lung injury through further exploration and more studies. https://inplasy.com/inplasy-2024-10-0115/, identifier INPLASY2024100115.

Chlamydomonas IC97, an intermediate chain of the flagellar dynein f/I1, is required for normal flagellar and cellular motility.

IDA f/I1 is a hetero-dimeric flagellar dynein that is particularly important for the regulation of flagellar waveform and whose defects are associated with human ciliopathies. IC97 is an evolutionarily conserved intermediate chain of IDA f/I1, but the detailed molecular functions of IC97 in flagellar motility have not been elucidated. In this study, mutational and biochemical analyses of the previously uncharacterized Chlamydomonas ic97 mutant revealed that IC97 is required for both the normal flagellar and cellular motility. In particular, IC97 appears to play an important role in both the control of flagellar beat frequency and the coordination between the two (cis- and trans-) flagella in Chlamydomonas. Our results provide important insights into the regulation of IDA-f/I1 activity by IC97 and the pathogenetic mechanisms of human ciliopathies caused by IDA-f/I1 defects.