Pulmonary embolism (PE) is a common and potentially fatal manifestation of venous thromboembolism, typically resulting from thrombus formation in the venous circulation and subsequent embolization to the pulmonary arterial tree. Its pathobiology reflects the convergence of venous stasis, hypercoagulability, and endothelial dysfunction, which together initiate a thrombo-inflammatory cascade involving coagulation factors, vascular cells, and innate immune pathways. Although PE thrombi have classically been characterized as fibrin- and erythrocyte-rich structures, accumulating evidence supports an active and regulatory role for platelets across key stages relevant to PE, including thrombus formation, embolization potential, clot stabilization, resolution, and recurrence. Anticoagulation remains the foundation of PE prevention and treatment, with low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants representing the main therapeutic options in contemporary practice. In contrast, the role of antiplatelet therapy in PE remains to be further investigated. While antiplatelet agents may provide modest benefit in selected clinical settings—such as specific prophylactic scenarios and secondary prevention after discontinuation of anticoagulation—their efficacy is generally inferior to anticoagulants, and they are not recommended as first-line therapy for acute PE management. Mechanistically, platelets can contribute to PE-related thrombogenesis by providing procoagulant surfaces, amplifying thrombin generation, and mediating crosstalk with endothelial and innate immune cells, particularly neutrophils and monocytes. These interactions promote immunothrombosis, neutrophil extracellular trap formation, and thrombus stabilization, reinforcing the link between inflammation and coagulation within the venous-to-pulmonary thromboembolic continuum. The primary objective of this review is to critically interpret the role of antiplatelet therapy specifically in PE by integrating recent preclinical insights with contemporary clinical evidence. By synthesizing advances in platelet biology, experimental models, and clinical studies, this article evaluates the therapeutic potential, limitations, and future directions of platelet-targeted strategies in PE. A deeper understanding of platelet-driven mechanisms may inform the development of safer, more precise antithrombotic approaches that complement established anticoagulant therapies and improve outcomes in patients with PE.
Metabolic dysfunction-associated steatotic liver disease is among the most prevalent chronic liver diseases worldwide. Its increasing incidence is typically linked to over-nutrition and metabolic syndrome. However, this account remains insufficiently detailed, particularly regarding diseases in lean individuals and the generational acceleration of metabolic illnesses. The exposome encompasses the entirety of the environmental exposure throughout an individual’s life and provides a complementary framework. The liver is a pivotal organ given that it is the primary location for the biotransformation of xenobiotics. This study synthesized data suggesting that environmental chemical exposure may be a plausible and controllable factor in steatotic liver disease while distinguishing associations from causation. We reviewed the main exposure classes, including per- and polyfluoroalkyl substances, micro- and nanoplastics, endocrine-disrupting plasticizers, persistent organic pollutants, hazardous metals, and air pollution. We assessed the strength of human evidence and delineated the potential mechanisms shared by these agents, including nuclear receptor disruption, mitochondrial and oxidative injury, inflammasome activation, stellate cell fibrogenesis, gut microbiota-bile acid disruption, and developmental reprogramming, along with their documented associations with steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma. The recognition of environmental exposure redefines metabolic dysfunction-associated steatotic liver disease as chemical environment-driven. These findings have implications in risk assessment, treatment, and prevention.
Bariatric surgery alters adipose tissue endocrine function; however, whether Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) produce different long-term adipokine profiles remains uncertain. This narrative mini-review summarizes head-to-head human evidence supported by mechanistic studies on leptin, adiponectin, resistin, and chemerin. Mid-term and long-term follow-up were defined as 6-12 months and ≥ 12 months, respectively. Both procedures consistently lower leptin levels and the best randomized evidence indicates comparable 12-month reductions when weight loss is similar. Furthermore, chemerin levels decreased after both surgeries, although comparative evidence is limited. Adiponectin increased after RYGB and LSG; several small cohort studies reported a greater increase after RYGB, whereas other studies found similar changes. However, evidence for the procedure-specific effects of resistin is sparse and inconsistent. Changes in adipokines correlate with insulin resistance and other metabolic risk markers; however, current studies have not established whether these biomarkers mediate durable diabetes remission, cardiovascular events, or liver outcomes. Baseline adiposity, diabetes status, postoperative weight loss, supplementation, assay methods, and study design preclude between-procedure comparisons. Adipokine measurements are, as yet, inadequate to guide procedure selection, and larger, longer, randomized studies with standardized assays are needed.
BACKGROUND To pick up liver fibrosis, prior to presenting with cirrhosis, several different risk scores exist. One such, the fibrosis-4 (FIB-4) score, was originally validated in a population with hepatitis C and human immunodeficiency virus infection and subsequently expanded to metabolic dysfunction-associated steatotic liver disease. Local and national (British) guidelines outline when deranged liver function tests warrant calculation of a FIB-4 score. AIM To investigate whether the population tested with FIB-4 locally resembled the validation group/if FIB-4 was applied according to guidelines. METHODS All FIB-4 requests in one month from two hospitals were collected from the local laboratory system, along with laboratory and demographic data. The data collected were narrowed down to those that matched the initial validation population’s laboratory values from 2006. The group was then further narrowed down to exclude patients dissimilar to the validation population (using electronic medical records to exclude based on age, obesity, and other factors as outlined by the original study from which the FIB-4 score originates). RESULTS It was found that the vast majority of patients having a FIB-4 calculated were grossly dissimilar to the initial population on which the score was originally validated, and the patients who did resemble it often had a FIB-4 calculated even if there was no apparent indication to do so. CONCLUSION There are multiple compounding factors of error in indiscriminate use of FIB-4. Probability of liver steatosis would likely be better assessed by using adaptations of the score on appropriate populations.
Insulin resistance, a pathophysiological response in metabolic syndrome, raises cancer risk. Mitochondrial dysfunction is a hallmark of cancer. The mitochondrial energetic profile of platelets in patients with cancer who have insulin resistance is unclear. Similarly, the profile of mitochondrial dysfunction in type 2 diabetes (T2-D) has not yet been published. The transmembrane protein in human adipose tissue known as dipeptidyl peptidase 4 (DPP4) is associated with T2-D secondary to obesity. Furthermore, DPP4 has been implicated in cancer pathogenesis. Studies have shown a connection between obesity and cancer. However, whether DPP4 inhibition ameliorates insulin resistance in patients with cancer has not been elucidated. This perspective aims to explore how platelet mitochondria fail in patients with cancer who have insulin resistance, discuss how blocking DPP4 might antagonize insulin resistance in cancer, and describe a cell culture model for obesity and insulin resistance. The available literature supports the proposal that patients with cancer and insulin resistance (or T2-D) have less active mitochondria in their platelets than patients with cancer without insulin resistance or healthy individuals. The platelet mitochondrial bioenergetic profile may signal early mitochondrial dysfunction in patients with cancer and insulin resistance. The proposed model is applicable to patients with T2-D and obesity.
Short-chain fatty acids (SCFAs) are metabolic products of bacterial fermentation of undigested/unabsorbed carbohydrates and fibers in the intestine. SCFAs are used by intestinal epithelial cells as an energy source and regulates several large-intestine functions, such as motility, visceral sensitivity, the immune system, and the gut barrier. About 95% of SCFAs are acetic, propionic, and butyric acids occurring in proportions of 60%: 20%: 20% in healthy subjects, while the proportion of butyric acid is lower than 20% in irritable bowel syndrome (IBS) patients. Acetic and propionic acids are not correlated with IBS symptoms, suggesting that they are not involved in symptom manifestation. The butyric acid level increased in IBS patients after fecal microbiota transplantation, and was inversely correlated with abdominal pain, diarrhea, and constipation. The effects of butyric acid on IBS symptoms such as abdominal pain, diarrhea, and constipation can be attributed to its modulation of the expression levels of serotonin, peptide YY, and glucagon-like peptide-1 in the intestinal enterochromaffin cells and L-cells. The butyric acid level was also inversely correlated with chronic fatigue, which occurs in about 54% of IBS patients. Treatment with sodium butyrate in capsule form is a promising therapeutic approach for IBS.
BACKGROUND Adipose-derived stromal cells (ADSCs) are a mixed cell population, which includes, amongst others, mesenchymal stromal cells (MSCs). The first choice of cell isolation is subcutaneous adipose tissue as it is easily accessible, abundant and easily harvested by a less invasive procedure. AIM To determine the viability and phenotypic properties of the ADSCs that are treated by two procedures to induce stromal vascular fraction (SVF) by lipoaspirate, to verify that they can be used to ensure safe and efficient repair of articular cartilage defects. METHODS Lipoaspirate samples of adipose tissues were taken using various commercially available systems of withdrawal. The cellular components of SFVs in untreated lipoaspirate samples were compared with similar cells obtained with the use of lipoaspirate samples treated with Lipogems® and Body-Jet® eco systems as a method of assessing cell composition and viability. The multicolour flow cytometry (FC) analysis was used to characterize the outputs. RESULTS Multicolour FC analysis revealed that SVF is composed of heterogeneous cell populations such as: (1) Adipose stem cells (CD45-CD90+CD73+CD34+ CD31- CD105-CD146-); (2) Endothelial progenitor cells (CD45-CD90+ CD73+CD34+ CD31+ CD105 LowCD146+); and (3) Pericytes (CD45-CD90+CD73+ CD34- CD31-CD105-CD146+), and other more or less characterized cells. The overall cell viability was similar across the groups. However, we observed a steady rise in the percentage of the endothelial cells and pericytes in the processed samples with Lipogems® and Body-Jet® eco systems in comparison to the untreated lipoaspirate samples. CONCLUSION Phenotypic characterization studies have suggested that MSC populations are found in a perivascular site with ADSCs shared with pericytes and endothelial cells. We have indications that the mechanical withdrawal steps can leave a large population heterogeneity of cells, retaining a more intricate tissue architecture (niche).
BACKGROUND An 83-year-old male with multiple comorbidities presented with high-output biliary leak following a subtotal cholecystectomy for acute cholecystitis. He was referred for advanced biliary intervention. CASE SUMMARY Despite repeated endoscopic retrograde cholangiopancreatography and the placement of up to three biliary plastic stents, the patient experienced an increase in bilious drainage reaching 200 mL/day, accompanied by significant weight loss. Magnetic resonance cholangiopancreatography revealed a fluid collection at the gallbladder bed connected to the biliary tree, confirming an active bile leak, likely originating from the cystic duct stump. At endoscopic retrograde cholangiopancreatography, the previously placed biliary stents were removed, and common bile duct (CBD) was selectively cannulated. Cholangiogram showed dilated CBD with a leak at the cystic duct. SpyGlass cholangioscope was used to cannulate the cystic duct, and a guidewire was passed through the leak site to the percutaneous drain. A biliary access cannula was inserted over the guidewire via the percutaneous route, and 3 coils (two of 4 mm and one of 6 mm) were deployed at the leak site, followed by cyanoacrylate glue injection. This achieved immediate and complete cessation of the leak, as confirmed by an occlusion cholangiogram. A 7-Fr 12-cm plastic biliary stent was placed into the CBD, and free flow of bile was noted, providing a minimally invasive solution for a refractory post-surgical complication. CONCLUSION This case highlights that for persistent, high-output stump leaks that fail conventional stenting, the combined use of cholangioscopy-guided coil and glue embolization offers an effective salvage therapy that avoids the morbidity of a second major surgery.
Rehabilitation protocols for various knee conditions and elective procedures are essential for restoring function and patient satisfaction, as these conditions are frequently associated with significant muscle strength loss and may eventually require prolonged recovery. This minireview highlights the adjunctive role of blood flow restriction (BFR) training in this context. The fundamental principles of BFR involve controlled external occlusion to induce physiological training effects with substantially reduced mechanical load. BFR was added to various rehabilitation protocols for patients with knee conditions, such as primary osteoarthritis and rheumatoid arthritis, and was also applied during the rehabilitation of patients undergoing knee-related surgical interventions, including anterior cruciate ligament reconstruction and total knee arthroplasty. Various studies, systematic reviews, and meta-analyses have shown the effectiveness of BFR in improving muscle strength and function, with added value for functional outcomes and patient satisfaction. Furthermore, it showed an acceptable safety profile. However, a clear description of the protocols for BFR, tailored to each patient and procedure, should be provided. Moreover, long-term data on BFR involvement in the rehabilitation protocols for different knee conditions and after various surgical procedures, compared with conventional rehabilitation protocols, are still required.
BACKGROUND Distal humerus fracture-related infections (FRIs), particularly those involving the articular surfaces of the elbow, pose a significant challenge as they can lead to severe upper limb functional impairment and systemic complications. Distal humerus fractures represent about 2% of all fractures and approximately 30% of all elbow fractures. Such kind of infections are reported in literature with rates from 4% to 14.5% of distal humerus fractures treated with open reduction and internal fixation. We analyzed current evidence on distal humerus FRIs and report our clinical approach aimed at achieving both fracture healing and infection eradication. AIM To present a consecutive series of distal humerus FRIs, and to synthesize treatment strategies and to propose a decision-making algorithm. METHODS We performed a retrospective analysis of 43 patients with distal humerus FRIs treated at our institution between 2017 and 2022. Patients were stratified according to fracture healing status and time from index surgery (early/delayed < 6 weeks; late > 6 weeks). Treatment strategies included debridement, antibiotics, and implant retention (DAIR), implant removal, or suppressive antibiotic therapy. Primary outcomes were infection eradication and fracture union. Based on these variables, a treatment algorithm was developed. RESULTS Among patients with healed fractures (n = 6), implant removal and debridement resulted in infection eradication in all cases (100%). In early/delayed infections (n = 6), DAIR achieved both fracture union and infection control in 100% of cases. In patients treated with implant removal for unhealed fractures (n = 19), infection eradication and fracture healing were achieved in 14 cases (73.7%), while 5 patients (26.3%) required conversion to total elbow arthroplasty. In cases managed with implant retention and suppressive antibiotic therapy (n = 12), infection control was maintained until fracture union in all patients. Mean follow-up was 45 months. DAIR was effective in resolving acute and delayed infections. For late infections, both eradication and suppression yielded satisfactory outcomes. CONCLUSION The literature on the management of distal humerus FRI is limited. Although limited by the small sample size and absence of a control group, the manuscript describes our approach to managing distal humerus FRIs, which could contribute to improved patient outcomes.
Parental consanguinity is associated with an increased risk of autosomal recessive disorders, some of which may present neurological and developmental impairment. In this issue, a retrospective cohort study from Jazan, Saudi Arabia, by Alhamoud et al , published in the World Journal of Clinical Pediatrics ”, evaluated the relationship between consanguinity and neurodevelopmental outcomes in pediatric patients and found no statistically significant association despite minor differences in clinical patterns. This finding highlights the challenges of detecting genetic effects within heterogeneous clinical populations, particularly when neurodevelopmental conditions include both monogenic and multifactorial etiologies. This editorial contextualizes these results within current genetic and epidemiological understanding, emphasizing that cohort-level findings may not fully capture underlying biological risk. It also outlines key clinical and public health considerations, including targeted developmental screening and culturally appropriate genetic counseling, and underscores the need for well-designed prospective studies incorporating genomic data and precise phenotyping.
BACKGROUND Tumor organoids are 3D cell culture models derived from patient tumor tissues that replicate the complexity of the tumor microenvironment (TME). These models preserve the genetic and phenotypic features of the original tumor, making them superior to traditional 2D cultures and xenografts for cancer research. AIM To explore the role of tumor organoids in translational cancer research, with a focus on their applications in personalized therapy and drug testing. METHODS A comprehensive review of studies was conducted, including articles from PubMed, Scopus, and Web of Science, with a focus on tumor organoid models in cancer research, particularly in preclinical and clinical drug testing, personalized therapy, and biomarker identification. RESULTS Tumor organoids enable high-throughput drug screening, allowing the identification of effective therapies for individual patients. They provide insights into tumor behavior, metastasis, and resistance mechanisms. Additionally, organoids facilitate the evaluation of various therapeutic strategies, including chemotherapy, targeted therapies, and immunotherapies. Despite challenges like inconsistent success rates and ethical concerns with animal-derived matrices, advancements in organoid technology, including AI integration and multi-omics, promise to enhance their clinical applications. CONCLUSION Tumor organoids hold immense potential in precision oncology by providing more accurate, patient-specific models for studying cancer biology and predicting treatment responses. Their integration into clinical decision-making will enhance personalized treatment approaches and improve cancer therapy outcomes.
BACKGROUND Acute ischemic stroke（AIS） is one of the major causes of the continuous increasing rate of global mortality due to the lack of timely diagnosis, prognosis, and management. This study provides a primitive platform for non-invasive and cost-effective diagnosis and prognosis of patients with AIS using circulating cellfree mitochondrial DNA（cf-mtDNA） quantification and validation.AIM To evaluate the role of cf-mtDNA as s non-invasive, and affordable tool for realtime monitoring and prognosticating AIS patients at disease onset and during treatment.METHODS This study enrolled 88 participants including 44 patients with AIS and 44 healthy controls with almost similar mean age group at stroke onset, and at 24 h and 72 h of treatment. Peripheral blood samples were collected from each study participant and plasma was separated using centrifugation. The cf-mtDNA concentration was quantified using nanodrop reading and validated through real-time quantitative polymerase chain reaction（RT-qPCR） of NADH-ubiquinone oxidoreductase chain 1（ND1） relative transcript expression levels.RESULTS Comparative analysis of cf-mtDNA concentration in patients at disease onset showed significantly increased levels compared to control individuals for both nanodrop reading, as well as ND1 relative expression levels（P ＜ 0.0001）.Intergroup analysis of cf-mtDNA concentration using nanodrop showed significantly reduced levels in patients at 72 h of treatment compared to onset（P ＜ 0.01）. However, RT-qPCR analysis showed a significant reduction at 24 h and 72 h of treatment compared to the disease onset（P ＜ 0.001）. The sensitivity and specificity were relatively higher for RT-qPCR than nanodrop-based cfmtDNA quantification. Correlation analysis of both cf-mtDNA concentration as well as ND1 relative expression with National Institute of Health Stroke Scale score at baseline showed a positive trend.CONCLUSION In summary, quantitative estimation of highly pure cf-mtDNA provides a simple, highly sensitive and specific, non-invasive, and affordable approach for real-time monitoring and prognosticating AIS patients at onset and during treatment.
Diabetes has been one of the major concerns in recent years, due to the increasing rate of morbidity and mortality worldwide. The available treatment strategies for uncontrolleddiabetesmellitus（DM）arepancreasorislettransplantation.However, these strategies are limited due to unavailability of quality pancreas/islet donors, life-long need of immunosuppression, and associated complications.Cell therapy has emerged as a promising alternative options to achieve the clinical benefits in the management of uncontrolled DM. Since the last few years, various sources of cells have been used to convert into insulin-producing β-like cells.These extrapancreatic sources of cells may play a significant role in β-cell turnover and insulin secretion in response to environmental stimuli. Stem/progenitor cells from liver have been proposed as an alternative choice that respond well to glucose stimuli under strong transcriptional control. The liver is one of the largest organs in the human body and has a common endodermal origin with pancreatic lineages. Hence, liver has been proposed as a source of a large number of insulinproducing cells. The merging of nanotechnology and 3D tissue bioengineering has openedanewdirectionforproducingislet-likecellssuitableforinvivo transplantation in a cordial microenvironment. This review summarizes extrapancreatic sources for insulin-secreting cells with reference to emerging technologies to fulfill the future clinical need.
Photobiomodulation（PBM） is a non-invasive therapeutic modality with demonstrated effects in many fields related to regenerative medicine. In the field of orthopedics, in particular, PBM at various wavelengths has demonstrated the capacity to trigger multiple biological effects associated with protective mechanisms in musculoskeletal tissues. The articles cited in this review show that devices operating close to or within the near infrared range at low intensities can provoke responses which favor the shift in the predominant catabolic microenvironment typically seen in degenerative joint diseases, especially osteoarthritis（OA）. These responses include proliferation, differentiation and expression of proteins associated with stable cell cycles. Additionally, PBM can also modulate oxidative stress, inflammation and pain by exerting regulatory effects on immune cells and blocking the transmission of pain through sensory neuron fibers, without adverse events. Collectively, these effects are essential in order to control the progression of OA, which is in part attributed to exacerbated inflammation and degradative enzymatic reactions which gradually contribute to the destruction of joint tissues. PBM may offer medical experts ease of application, financial viability, efficacy and lack of serious adverse events. Therefore, it may prove to be a suitable ally in the management of mild to moderate degrees of OA. This review explores and discusses the principal biological mechanisms of PBM and how the produced effects may contribute to the amelioration of osteoarthritic progression. Literature was reviewed using Pub Med and Google Scholar in order to find studies describing the mechanisms of PBM. The investigation included a combination of nomenclature such as: “photobiomodulation”, “phototherapy”, “laser therapy”, “PBM”, “osteoarthritis”, low level light therapy”, “inflammation” and “cartilage”. We considered only articles written in English, with access to the full text.
Despite various advances in cancer research, the incidence and mortality rates of malignant diseases have remained high. Accurate risk assessment, prevention, detection, and treatment of cancer tailored to the individual are major challenges in clinical oncology. Artificial intelligence（AI）, a field of applied computer science, has shown promising potential of accelerating evolution of healthcare towards precision oncology. This article focuses on highlights of the application of data-driven machine learning（ML） and deep learning（DL） in translational research for cancer diagnosis, prognosis, treatment, and clinical outcomes. MLbased algorithms in radiological and histological images have been demonstrated to improve detection and diagnosis of cancer. DL-based prediction models in molecular or multi-omics datasets of cancer for biomarkers and targets enable drug discovery and treatment. ML approaches combining radiomics with genomics and other omics data enhance the power of AI in improving diagnosis, prognostication, and treatment of cancer. Ethical and regulatory issues involving patient confidentiality and data security impose certain limitations on practical implementation of ML in clinical oncology. However, the ultimate goal of application of AI in cancer research is to develop and implement multi-modal machine intelligence for improving clinical decision on individualized management of patients.
Cardiovascular disease（CVD） has been associated with the so-called traditional risk factors, such as hypertension, hypercholesterolemia and cigarette smoking.Chronic inflammation, exemplified by elevated high sensitivity C-reactive protein, has been added to these risk factors for CVD as non-traditional risk factor. There are two aspects in this association. The first is whether inflammation plays a pathogenic role in traditional risk factors-mediated CVD or it is just an epiphenomenon. The second is whether chronic inflammation caused by an inflammatory disease has any impact on CVD. Accumulated data have shown that inflammation has a central and inciting role in the development of atherosclerosis leading to increased CVD risk. How inflammation contributes to CVD is a topic of continuous research where mechanisms involving both innate and adaptive immune pathways are involved. Endothelial dysfunction, oxidative stress in vascular endothelial cells, macrophage accumulation, formation of inflammasome, production of tumor necrosis factor（TNF）-a, IL-1 and IL-6 characterize the inflammatory process leading to atherogenesis. Recently clonal hematopoiesis of indeterminate potential represents a surprising and novel mechanism underlying atherogenesis. Data from chronic rheumatic inflammatory diseases exemplify the complexity of mechanisms leading to increased CVD, while they also provide evidence that anti-inflammatory biologic drugs, such as anti-TNF and anti-IL6 agents, could control atherogenesis and ameliorate CVD risk. Recent groundbreaking work using biologic anti-IL-1 b therapy to treat men and women who have had a prior heart attack provides the best proof of the pathogenic contribution of inflammation in the development of CVD.
Although boron has been a chemical element of interest since the ancient times,only a few boron-containing compounds（BCCs）had been used for medicinal purposes before the 21 st century.Among these,only boric acid has been explored in multiple therapeutic applications.Hence,it is common to extrapolate from boric acid to all BCCs,supposing a similar biological effect.However,boric acid is just one of dozens of BCCs in nature and thousands available from chemical synthesis.Nowadays,there is a boom in research on new BCCs as potential tools in the prevention,diagnosis and therapy of human disease.We herein discuss the new role of BCCs in drug development,with emphasis on the compounds for which a mechanism of action has been proposed or demonstrated.Because of data gathered in recent years,BCCs have expanded beyond the well-known fields of antimicrobial and antineoplastic agents,now being explored for their possible use as enzyme inhibitors,regulators of protein expression and modulators of the immune response,as well as in biomaterials.We suggest that translational medicine can accelerate the medicinal applications of BCCs,which is especially important for the human diseases that are generating a high global burden.
