Tissue Damage Research Articles

Targeting Nrf2 signaling in dry eye

Dry eye, the most common ocular surface disease, can cause ocular surface tissue damage and discomfort symptoms and seriously affect people’s quality of life. The etiology of dry eye is diverse, and its pathogenesis is complex. The oxidative stress reaction is considered to be among the important factors in the pathogenesis of dry eye. Therefore, activating the antioxidant system has a potential therapeutic effect on dry eye. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is considered the most important antioxidant pathway in the body. The activation of the Nrf2 signaling pathway and its interaction with other pathways are important mechanisms to prevent the occurrence and development of dry eye. This review describes the structure and function of Nrf2, summarizes the changes in the oxidative stress response in dry eye, focuses on the potential mechanism of the Nrf2 signaling pathway in the treatment of dry eye, and, finally, summarizes the drugs that activate the Nrf2 signaling pathway in the treatment of dry eye.

Sirtuins and mechanisms of diabetic lung damage: a scientific discussion. A review

Induced tissue damage in target organs (kidneys, heart, eyes, liver, skin, nervous system) significantly contributes to the morbidity and mortality of patients from diabetes mellitus (DM). In recent decades, the question has been actively discussed: should the lungs be regarded as a target organ for diabetes? The c collected data demonstrate histological and functional lung disorders in DM patients. This suggests that the lungs are a target organ for diabetes. It is known that sirtuins regulate a number of physiological processes and affect obesity, insulin resistance, type 2 DM, heart disease and aging. In this review, we have tried to summarize the knowledge about the contribution of sirtuins to cellular regulation and the formation of pulmonary disease in patients with type 2 DM.

Absence of genotoxicity following pulmonary exposure to metal oxides of copper, tin, aluminum, zinc, and titanium in mice.

Inhalation of nanosized metal oxides may occur at the workplace. Thus, information on potential hazardous effects is needed for risk assessment. We report an investigation of the genotoxic potential of different metal oxide nanomaterials. Acellular and intracellular reactive oxygen species (ROS) production were determined for all the studied nanomaterials. Moreover, mice were exposed by intratracheal instillation to copper oxide (CuO) at 2, 6, and 12 μg/mouse, tin oxide (SnO2) at 54 and 162 μg/mouse, aluminum oxide (Al2O3) at 18 and 54 μg/mouse, zinc oxide (ZnO) at 0.7 and 2 μg/mouse, titanium dioxide (TiO2) and the benchmark carbon black at 162 μg/mouse. The doses were selected based on pilot studies. Post-exposure time points were 1 or 28 days. Genotoxicity, assessed as DNA strand breaks by the comet assay, was measured in lung and liver tissue. The acellular and intracellular ROS measurements were fairly consistent. The CuO and the carbon black bench mark particle were potent ROS generators in both assays, followed by TiO2. Al2O3, ZnO, and SnO2 generated low levels of ROS. We detected no increased genotoxicity in this study using occupationally relevant dose levels of metal oxide nanomaterials after pulmonary exposure in mice, except for a slight increase in DNA damage in liver tissue at the highest dose of CuO. The present data add to the body of evidence for risk assessment of these metal oxides.

Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4+ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4+ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.

Infectious Complications in Pediatric Hematopoietic Stem Cell Transplantation Recipients in Northeast Mexico

Abstract Background Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for an increasing number of neoplastic and hematological diseases. However, these patients are at high risk of acquiring infections due to a complex interaction involving organ dysfunction, tissue damage, pathogen exposure, pathogen virulence, and the overall state of dynamic immunosuppression varying according to different phases of immunologic reconstitution after HSCT, and the need for immunosuppressants to prevent and treat non-infectious complications such as graft-versus-host disease (GVHD). Methods All patients under 16 years old who underwent HSCT at the “Dr. José Eleuterio González” University Hospital, a referral center in Northeast Mexico, from March 2019 to October 2023, were included. Clinical, epidemiological, and analytical characteristics of the patients and infectious episodes during pre-engraftment, early engraftment, and late engraftment periods were analyzed. Results In the studied period, a total of 75 patients underwent HSCT, of whom 52 (69%) experienced infectious events (IEs). A total of 136 IEs were documented, averaging 2.5 IEs per patient. Among these, 40% were viral infections, 33% bacterial, 6.6% fungal, 0.7% parasitic, and 19.3% were indeterminate. The most prevalent baseline diagnoses were acute lymphoblastic leukemia (52%), acute myeloid leukemia (19%), and aplastic anemia (12%). Seventy-two percent of the patients underwent a haploidentical stem cell transplantation, and the graft was sourced from peripheral blood stem cells in 75% of the population. Bacterial infections were predominant in the pre-engraftment period, whereas viral infections were more frequent in early and late engraftment. The distribution of these IEs by period is shown in Figure 1. Among bacterial infections, bloodstream infections (BSIs) accounted for 56%, followed by skin and soft tissue infections (14%) and gastroenteritis (13%). Of the 26 BSI events, 73% were caused by Gram-negative bacilli, including 8 cases of Escherichia coli (42%), 6 cases of Pseudomonas aeruginosa (32%), 2 cases of Klebsiella pneumoniae (11%), and 1 case each of Acinetobacter calcoaceticus, Salmonella enterica and Stenotrophomonas maltophilia (5%). 44% of these exhibited extended-spectrum beta-lactamase (ESBL), and 19% were carbapenem-resistant. The remaining 27% of BSI were caused by Gram-positive cocci: Staphylococcus epidermidis (43%), Streptococcus viridans group (29%), Staphylococcus aureus, and Rothia mulcilaginosa (14% each). 17% of all BSI were central line associated bloodstream infection (CLABSI). Among viral infections, cytomegalovirus (CMV) was the most frequent agent at 46%, followed by SARS-CoV-2 and BK virus at 14% and 11%, respectively. Among the fungal infections, we identified 9 cases of invasive fungal disease (IFD), four cases of possible IFD, two of probable IFD and three cases of proven IFD were identified, including one case each of mucormycosis (zygomycetes), Candida tropicalis fungemia, and Aspergillus niger pneumonia. Additionally, one case of intestinal giardiasis, was identified, accounting for 0.7% of the total. Conclusion Infections represent one of the major adverse events in patients undergoing HSCT. It is essential to understand the local epidemiology in each hospital center to tailor international guidelines to the available resources in each institution, which is crucial in improving strategies for preventing, detecting, and providing timely treatment for these infectious complications and their clinical outcomes. Figure 1. Distribution of infectious events among the post-HSTC periods.

Unraveling Mitochondrial Reactive Oxygen Species Involvement in Psoriasis: The Promise of Antioxidant Therapies

Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and aberrant keratinocyte proliferation. Despite tremendous advances in understanding its etiology, effective therapies that target its fundamental mechanisms remain necessary. Recent research highlights the role of reactive oxygen species dysregulation and mitochondrial dysfunction in psoriasis pathogenesis. Mitochondrial reactive oxygen species mediate cellular signaling pathways involved in psoriasis, such as proliferation, apoptosis, and inflammation, leading to oxidative stress, exacerbating inflammation and tissue damage if dysregulated. This review explores oxidative stress biomarkers and parameters in psoriasis, including myeloperoxidase, paraoxonase, sirtuins, superoxide dismutase, catalase, malondialdehyde, oxidative stress index, total oxidant status, and total antioxidant status. These markers provide insights into disease mechanisms and potential diagnostic and therapeutic targets. Modulating mitochondrial reactive oxygen species levels and enhancing antioxidant defenses can alleviate inflammation and oxidative damage, improving patient outcomes. Natural antioxidants like quercetin, curcumin, gingerol, resveratrol, and other antioxidants show promise as complementary treatments targeting oxidative stress and mitochondrial dysfunction. This review aims to guide the development of personalized therapeutic methods and diagnostic techniques, emphasizing the importance of comprehensive clinical studies to validate the efficacy and safety of these interventions, paving the way for more effective and holistic psoriasis care.

The PANoptosis-related hippocampal molecular subtypes and key biomarkers in Alzheimer’s disease patients

Alzheimer’s Disease (AD) is a neurodegenerative disorder, and various molecules associated with PANoptosis are involved in neuroinflammation and neurodegenerative diseases. This work aims to identify key genes, and characterize PANoptosis-related molecular subtypes in AD. Moreover, we establish a scoring system for distinguishing PANoptosis molecular subtypes and constructing diagnostic models for AD differentiation. A total of 5 hippocampal datasets were obtained from the Gene Expression Omnibus (GEO) database. In total, 1324 protein-encoding genes associated with PANoptosis (1313 apoptosis genes, 11 necroptosis genes, and 31 pyroptosis genes) were extracted from the GeneCards database. The Limma package was used to identify differentially expressed genes. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify gene modules significantly associated with AD. The ConsensusClusterPlus algorithm was used to identify AD subtypes. Gene Set Variation Analysis (GSVA) was used to assess functional and pathway differences among the subtypes. The Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine Recursive Feature Elimination (SVM-RFE) algorithms were used to select the three PANoptosis-related Key AD genes (PKADg). A scoring model was constructed based on the Boruta algorithm. PANoptosis diagnostic models were developed using the RF, SVM-RFE, and Logistic Regression (LR) algorithms. The ROC curves were used to assess the model performance. A total of 48 important genes were identified by intersecting 725 differentially expressed genes and 2127 highly correlated module genes from WGCNA with 1324 protein-encoding genes related to PANoptosis. Machine learning algorithms identified 3 key AD genes related to PANoptosis, including ANGPT1, STEAP3, and TNFRSF11B. These genes had strong discriminatory capacities among samples, with Receiver Operating Characteristic Curve (ROC) analysis indicating Area Under the Curve (AUC) values of 0.839, 0.8, and 0.868, respectively. Using the 48 important genes, the ConsensusClusterPlus algorithm identified 2 PANoptosis subtypes among AD patients, i.e., apoptosis subtype and mild subtype. Apoptosis subtype patients displayed evident cellular apoptosis and severe functionality damage in the hippocampal tissue. Meanwhile, mild subtype patients showed milder functionality damage. These two subtypes had significant differences in apoptosis and necroptosis; however, there was no apparent variation in pyroptosis functionality. The scoring model achieved an AUC of 100% for sample differentiation. The RF PANoptosis diagnostic model demonstrated an AUC of 100% in the training set and 85.85% in the validation set for distinguishing AD. This study identified two PANoptosis-related hippocampal molecular subtypes of AD, identified key genes, and established machine learning models for subtype differentiation and discrimination of AD. We found that in the context of AD, PANoptosis may influence disease progression through the modulation of apoptosis and necrotic apoptosis.

Candidate Molecular Biomarkers of Traumatic Brain Injury: A Systematic Review

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability among young and middle-aged individuals. Adequate and timely diagnosis of primary brain injuries, as well as the prompt prevention and treatment of secondary injury mechanisms, significantly determine the potential for reducing mortality and severe disabling consequences. Therefore, it is crucial to have objective markers that indicate the severity of the injury. A number of molecular factors—proteins and metabolites—detected in the blood immediately after trauma and associated with the development and severity of TBI can serve in this role. TBI is a heterogeneous condition with respect to its etiology, clinical form, and genesis, being accompanied by brain cell damage and disruption of blood–brain barrier permeability. Two oppositely directed flows of substances and signals are observed: one is the flow of metabolites, proteins, and nucleic acids from damaged brain cells into the bloodstream through the damaged blood–brain barrier; the other is the infiltration of immune cells (neutrophils and macrophages) and serological proteins. Both flows aggravate brain tissue damage after TBI. Therefore, it is extremely important to study the key signaling events that regulate these flows and repair the damaged tissues, as well as to enhance the effectiveness of treatments for patients after TBI.

Mussel-inspired thermo-switchable underwater adhesive based on a Janus hydrogel

On-demand underwater adhesives with excellent adhesive and gentle detachment properties enable stable connections to various biomedical devices and biointerfaces and avoid the risk of harmful tissue damage upon detachment. Herein, we present a Janus hydrogel adhesive that can reversibly switch its adhesion strength, which is controlled by temperature, using a thermoresponsive polymer and mussel-inspired molecules. This thermoswitchable adhesive (TSA) hydrogel displays both strong adhesion and gentle detachment with an over 1000-fold gap in underwater adhesion strength onto glass, titanium, aluminum, and Teflon substrates when exposed to temperatures above and below the lower critical solution temperature (LCST). The adhesion switch is possibly caused by the change in toughness of the TSA hydrogels with temperature because the Janus hydrogel possesses gradient crosslinked structures. Moreover, the lowermost surface is sufficiently soft to gently detach from the substrate below the LCST. The electrode-integrated hydrogel remains on human skin, and electrical signals are continuous over 10 min above the LCST. In contrast, commercially available hydrogel electrodes quickly swell and detach from the skin. The thermoswitchability of the TSA hydrogel, with its robust adhesion and gentle detachment, offers significant potential for biomedical applications characterized by minimally invasive procedures.

Microbiological bases of obsessive‑compulsive disorder - the role of viruses, bacteria, and parasites in the onset and progression of OCD.

Obsessive‑compulsive disorder (OCD) is a current topic of discussion nowadays. OCD presents a variety of different etiologies including environmental, viral, cognitive, or genetic aspects. In this article, we focused on the possible correlation between various infectious diseases as well as generally the relationship between viruses, bacteria, and parasites, and an increased OCD risk. In this narrative review, we analyzed different types of articles found on PubMed, Google Scholar, and Scopus, as well as the articles of the National Institute of Mental Health. Searching criteria included articles from 1991 till the end of November, research involving human and animal patients (including monkeys and rats), and research published in English. Research showed a relationship between Herpes simplex virus, Rubella virus, Human immunodeficiency virus, Borna disease virus, Mycoplasma pneumoniae, Toxoplasma gondii, streptococcal infections, as well as gut microbiota and increased OCD risk. The possible mechanisms of this relation include neuroinflammation, brain tissue damage, autoimmune processes, and impairments in neurotransmitter levels. Infections caused by Varicella zoster virus, Measles virus, Mumps virus, Epstein‑Barr virus, Cytomegalovirus, or Borrelia Burgdorferi may also contribute to the increased risk of OCD. Reports showed an increased frequency of OCD occurrence in a group of infected people compared to a healthy group. However, there is no evidence of the influence of Influenza virus, Coxsackie virus, Poliovirus, Parvovirus B19, Enterovirus 71, West Nile virus, Treponema Pallidum, or Toxocara infections on the OCD risk. There is a significant relationship between various infectious diseases and an increased OCD risk. However, further studies are crucial to discover the exact pathomechanisms of these correlations and the potential influence of other pathogens on the onset of OCD.

A Scientific Program in Regenerative Engineering (ASPIRE): A Prospective Program Aimed at Tackling Health Disparities in the USA.

The continued low numbers of Blacks in STEMM (Science, Technology, Engineering, Mathematics, and Medicine) represent an American crisis that threatens growing awareness and efforts to effectively address health disparities that affect the Black population. Regenerative engineering is an emerging STEMM field that seeks to combine principles from engineering, life sciences, physics, and medicine to develop new technologies for repairing and regenerating damaged tissues and organs. We believe that regenerative engineering has the potential to address some of the root causes of health disparities by developing new approaches that are more accessible and affordable, particularly for low-income communities and people living in rural areas. We have developed a new education program targeting to K-12 groups "A Scientific Program in Regenerative Engineering (ASPIRE)" that supports the mentoring and education of Black K-12 students to enter successfully and thrive as professionals in STEMM particularly in the area of regenerative engineering. We have been collaborating with several public-school systems in Connecticut, especially among the regions with health disparities to implement the program. We believe our new educational K-12 program would serve as a vehicle to reduce health disparities in the region.

Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury

Progranulin (PGRN), which is produced in neurons and microglia, is a neurotrophic and anti-inflammatory glycoprotein. Human loss-of-function mutations cause frontotemporal dementia, and PGRN knockout (KO) mice are a model for dementia. In addition, PGRN KO mice exhibit severe phenotypes in models of traumatic or ischemic central nervous system (CNS) disorders, including traumatic brain injury (TBI). It is unknown whether restoration of progranulin expression in neurons (and not in microglia) might be sufficient to prevent excessive TBI-evoked brain damage. To address this question, we generated mice with Nestin-Cre-driven murine PGRN expression in a PGRN KO line (PGRN-KONestinGrn) to rescue PGRN in neurons. PGRN expression analysis in primary CNS cell cultures from naïve mice and in (non-) injured brain tissue from PGRN-KONestinGrn revealed expression of PGRN in neurons but not in microglia. After experimental TBI, examination of the structural brain damage at 5 days post-injury (dpi) showed that the TBI-induced loss of brain tissue and hippocampal neurons was exacerbated in PGRN-KOGrnflfl mice (PGRN knockout with the mGrn fl-STOP-fl allele, Cre-negative), as expected, whereas the tissue damage in PGRN-KONestinGrn mice was similar to that in PGRN-WT mice. Analysis of CD68+ immunofluorescent microglia and Cd68 mRNA expression showed that excessive microglial activation was rescued in PGRN-KONestinGrn mice, and the correlation of brain injury with Cd68 expression suggested that Cd68 was a surrogate marker for excessive brain injury caused by PGRN deficiency. The results show that restoring neuronal PGRN expression was sufficient to rescue the exacerbated neuropathology of TBI caused by PGRN deficiency, even in the absence of microglial PGRN. Hence, endogenous microglial PGRN expression was not essential for the neuroprotective or anti-inflammatory effects of PGRN after TBI in this study.Graphical

Continuous Theta Burst Stimulation Inhibits Oxidative Stress-Induced Inflammation and Autophagy in Hippocampal Neurons by Activating Glutathione Synthesis Pathway, Improving Cognitive Impairment in Sleep-Deprived Mice.

Sleep deprivation (SD) has been reported to have a negative impact on cognitive function. Continuous theta burst stimulation (cTBS) shows certain effects in improving sleep and neurological diseases, and its molecular or cellular role in SD-induced cognition impairment still need further exploration. In this study, C57BL/6 mice were subjected to 48h of SD and cTBS treatment, and cTBS treatment significantly improved SD-triggered impairment of spatial learning and memory abilities in mice. Additionally, cTBS reduced malondialdehyde levels, increased superoxide dismutase activities, and inhibited the production of inflammatory cytokines, alleviating oxidative stress and inflammation levels in hippocampal tissues of SD model mice. cTBS decreased LC3II/LC3I ratio, Beclin1 protein levels, and LC3B puncta intensity, and elevated p62 protein levels to suppress excessive autophagy in hippocampal tissues of SD-stimulated mice. Then, we proved that inhibiting oxidative stress alleviated inflammation, autophagy, and death of hippocampal neuron cells through an in vitro cellular model for oxidative stress, and cTBS treatment promoted the production of glutathione (GSH), the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expression of GSH synthesis-related genes to enhance antioxidant capacity in hippocampal tissues of SD mice. An Nrf2 inhibitor ML385 or a GSH synthesis inhibitor BSO reversed the alleviating effects of cTBS treatment on oxidative stress-associated damage of hippocampal tissues and cognitive impairment in SD model mice. Altogether, our study demonstrated that cTBS mitigates oxidative stress-associated inflammation and autophagy through activating the Nrf2-mediated GSH synthesis pathway, improving cognitive impairment in SD mice.

Characterization of Extraintestinal Pathogenic Escherichia coli Strains Causing Canine Pneumonia in China: Antibiotic Resistance, Virulence Genes, and Sequence Typing

To determine the etiological agents responsible for acute pneumonia in puppies in China, this study utilized bronchoalveolar lavage (BAL) fluid extraction to enable the isolation, culture, biochemical identification, and 16S rRNA PCR amplification of the pathogens. Following preliminary identification, the pathogens underwent analysis for antibiotic resistance phenotypes and resistance genes. Additionally, the study examined the presence of virulence genes, conducted multilocus sequence typing (MLST), and performed whole-genome sequencing (WGS). The findings revealed that all four isolated pathogens were characterized as extraintestinal pathogenic Escherichia coli (ExPEC). The examined ExPEC strains demonstrated resistance to cephalosporins, tetracyclines, and penicillins, while remaining susceptible to aminoglycosides, beta-lactamase inhibitors, carbapenems, chloramphenicols, and sulfonamides. An analysis of virulence genes identified the presence of eight genes, namely CNF-I, fyuA, fimC, papC, ompA, fimH, irp2, and iroN, which are implicated in their invasiveness and potential to inflict tissue damage. The MLST analysis revealed that all ExPEC strains were classified under either sequence type ST131 (Achtman database) or ST43 (Pasteur database). The study further determined that these strains were absent in the kennel’s drinking water source, thereby ruling out water contamination as a potential factor in the emergence of ST131-type ExPEC. This study offers a theoretical framework and empirical evidence for elucidating the potential pathogenic mechanisms and clinical therapeutic strategies of ExPEC in the etiology of acute pneumonia in puppies.

Implementation of spirometry screening for post-tuberculosis lung disease (PTLD) among adolescents and adults enrolled within the National Tuberculosis Control Program of Carmelo Hospital in Chókwè District, Mozambique: A hybrid type III effectiveness-implementation study protocol

BackgroundDespite receiving adequate treatment, many tuberculosis (TB) survivors are left with post-tuberculosis complications, possibly due to lung tissue damage incurred during the active period of the disease. Current TB programs worldwide deliver quality care throughout the course of active TB treatment, yet often fail to provide organized follow-up once treatment ends. Post-tuberculosis lung disease (PTLD) is a prominent, yet underrecognized cause of chronic lung disease, managed similarly to chronic respiratory diseases with pharmacotherapy and/or personalized pulmonary rehabilitation interventions. Basic pulmonary rehabilitation packages for people finishing TB treatment are still lacking in low- and middle-income countries (LMICs). We offer a study protocol to evaluate the implementation of spirometry and symptom screening for PTLD among people who have completed TB treatment in a rural district in Mozambique.MethodsThe overall objective of this study is to evaluate the introduction of a new screening program that utilizes symptom screening and spirometry for diagnosing PTLD among adolescents and adults that have completed TB treatment. This research protocol consists of three complementary components: 1) assessing the prevalence of PTLD among patients enrolled in the National TB Control Program (NTCP) at Carmelo Hospital (CHC) in Chókwè District, Mozambique; 2) evaluating anticipated implementation outcomes through the identification of the site-, provider-, and individual-level determinants that either facilitate or hinder the successful adoption, implementation, and maintenance of the spirometry screening program, and 3) evaluating the real-time implementation outcomes/processes in order to provide practical evidence-based key indicators of successful implementation of the spirometry screening program.DiscussionProviding well-organized, evidence-based care for individuals with a history of TB who are experiencing symptoms of PTLD can relieve chronic respiratory issues, enhance quality of life, and potentially lower the risk of further pulmonary infections, including recurrent TB. However, there is a significant gap in the literature regarding the implementation of best practices of HIV and TB health services delivery. Addressing this gap could assist Mozambique in improving diagnosis, treatment, and continuity of care for people formerly living with TB. The insights from this study will help decision-makers improve spirometry screening coverage, enhance intervention effectiveness, and translate our findings to evidence-based programming.Trial registrationISRCTN92021748 retrospectively registered.

Acute Corrosive Acid Ingestion: A Case Series of Four Autopsies

Acute corrosive acid ingestion presents significant challenges in clinical and forensic pathology due to its severe and often fatal outcomes. This case series examines four autopsies involving fatal acid ingestion: three cases of hydrochloric acid (HCl) poisoning and one case of sulfuric acid (H₂SO₄) poisoning. Each case provides detailed autopsy findings, focusing on macroscopic and microscopic pathological changes. The first three cases of HCl poisoning revealed extensive tissue damage characterized by coagulative necrosis, particularly affecting the esophagus, stomach, and duodenum. Histological examination showed dense inflammatory infiltrate, submucosal edema, and significant hemorrhage, with patchy necrosis observed in the liver and kidneys. Pulmonary findings included alveolar edema and hemorrhage. The fourth case, involving H₂SO₄ ingestion, demonstrated more severe injuries with transmural necrosis and extensive hemorrhagic infiltration in the esophagus. The stomach exhibited full-thickness necrosis with a pronounced sulfurous odor, indicating severe chemical injury. Histopathological findings included extensive tissue dehydration and charring, with severe alveolar edema and hemorrhage in the lungs and extensive necrosis in the liver and kidneys. Comparative analysis of the histopathological changes highlighted the differences in tissue damage caused by these two acids. HCl primarily induced superficial necrosis with relatively preserved tissue architecture, while H₂SO₄ caused more extensive and deeper tissue damage due to its strong dehydrating and exothermic properties. Recognizing these differences is crucial for forensic pathologists in accurately diagnosing and differentiating cases of acid poisoning, ultimately enhancing diagnostic precision and clinical outcomes. This study underscores the severe and often fatal consequences of acute acid ingestion and aims to enhance the understanding of the pathological changes associated with such poisonings, thereby improving forensic and clinical evaluations.

Post-viral symptoms and conditions are more frequent in COVID-19 than influenza, but not more persistent

BackgroundPost-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as influenza.MethodsWe investigated a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last influenza outbreak in 2018 and followed them up to 18 months.ResultsWe found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the influenza or contemporary control cohort. The persistence of post-viral symptoms was similar between COVID-19 and influenza.ConclusionPost-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms.

Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis.

Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity. In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase. Using T1 relaxation time maps, lesions were categorized in long-T1 and short-T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w-MPRAGE lesion values. Rim visibility (VCLS analysis) was associated with increasing lesional T1 (P/PFDR < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long-T1 PRL were older than short-T1 PRL (average 0.8 vs. 2.0 years, P/PFDR = 0.005/0.008), and featured larger lesional volume (P/PFDR < 0.0001) and multi-shell diffusion-measured axonal damage (P/PFDR < 0.0001). The total volume of long-T1-PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/PFDR = 0.003/0.005 vs. P/PFDR = 0.042/0.057) and severity (MSSS; P/PFDR = 0.0006/0.001 vs. P/PFDR = 0.004/0.007). In random forest, having ≥1 long-T1-PRL versus ≥4 PRL showed 2-4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long-T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS. PRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long-T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure and function of lymphoid organs, while subsequent radiotherapy, chemotherapy, and lymph node dissection further damage the patient's immune system, leading to immune dysfunction, metabolic disorders, and increased susceptibility to infection, which seriously affect the patient's prognosis and quality of life. In this context, nanotechnology plays a key role in lymphoid organ regeneration and immune function recovery, including improving the therapeutic effect through targeted drug delivery systems, using targeted imaging probes to achieve tumor prediction and early detection, combining nanoplatforms with immunotherapy and photodynamic therapy to achieve synergistic therapeutic effects, and using nanomaterials to regulate the tumor microenvironment to enhance the sensitivity of traditional treatments. In addition, biophysical simulation strategies that simulate the microenvironment of lymphoid organs have also attracted widespread attention, aiming to construct a native cell environment to support the regeneration and functional recovery of damaged lymphoid tissues, or to simulate immune cells to regulate lymphocytes and induce specific immune responses. The multifaceted application of nanotechnology provides promising prospects for lymphoid organ regeneration and immune system repair.

Erxian decoction ameliorates myocardial tissue damage through activating PI3K/AKT signaling pathway in ovariectomized rats

Background Erxian decoction (EXD) is an empirical formula for treating cardiovascular disease, our previous work has shown that EXD could improve the cardiovascular structure and function in ovariectomized (OVX) rats, but its pharmacological mechanism is still unclear. Materials and Methods Network pharmacology was utilized to assess the key active components and central targets of EXD in treating postmenopausal cardiovascular disease. Then, an OVX rat model was established, HE staining and transmission electron microscope were utilized to observe myocardial tissue morphology, TUNEL staining was utilized to detect cardiomyocyte apoptosis, western blot, and ELISA were used to confirm efficacy and pathway of EXD. Results The network pharmacology prediction results showed that 129 common targets were identified by intersecting EXD targets and postmenopausal cardiovascular disease targets, including AKT1, TNF, IL-6, IL-1β, PTGS2 and other core targets, apoptosis, PI3K/AKT, and other signaling pathways may be closely related to postmenopausal cardiovascular disease. After ovariectomy, the myocardial tissue of rats was damaged, the expression level of PI3K/AKT pathway-related molecules in the myocardial tissue were decreased, the apoptosis index of cardiomyocytes was increased, and the levels of inflammatory factors (TNF-α, IL-6, and IL-1β) were enhanced. EXD intervention could improve myocardial tissue injury, EXD could up-regulate the protein expression of PI3K and p-AKT in myocardial tissue, and thereby prevent myocardial cell apoptosis. At the same time, EXD downregulated the levels of inflammatory factors in serum of ovariectomized rats. Conclusion EXD may prevent myocardial tissue damage through induction of the PI3K/AKT signaling pathway, thereby reducing cardiomyocyte apoptosis and inflammation. EXD may be a potential drug for the treatment of postmenopausal cardiovascular disease.