Search Results (245)

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

The complex microenvironment of wounds, along with challenges such as microbial infections, tissue damage, and inflammatory responses during the healing process, renders wound repair a complex medical issue. Owing to their ease of administration, effective outcomes, and painless application, biomacromolecule-based wound dressings have become a focal point in current clinical research. In recent years, hydrogels, microneedles, and electrospun nanofibers have emerged as three novel types of wound dressings. By influencing various stages of healing, they have notably enhanced chronic wound healing outcomes and hold considerable potential for wound repair applications. This review describes the preparation methods, classification, and applications of hydrogels, microneedles, and electrospun nanofibers around the various stages of wound healing, clarifying the healing-promoting mechanisms and characteristics of the three methods in different stages of wound healing. Building upon this foundation, we further introduce smart responsiveness, highlighting the application of stimuli-responsive wound dressings in dynamic wound management, aiming to provide insights for future research. Full article

Objective: The interactions between the central nervous system (CNS) and the immune system suggest that immune mechanisms may be effective in the pathogenesis of epilepsy and epileptic seizures. Although studies on the natural immune response and epilepsy are continuing, it is not yet clear whether the interaction of the current immune system is due to epilepsy itself or antiepileptic drugs (AEDs), since epileptic patients also use AEDs There are a limited number of studies that have reported an increased incidence of upper respiratory tract infections (URTIs) in patients during levetiracetam (LEV) treatment. Therefore, we aimed to report our experience regarding the effect of LEV monotherapy on the complete blood count (CBC), immunoglobulin (Ig) levels, and lymphocyte subgroups in the interictal period in children and adolescents with epilepsy. Methods: This study enrolled 31 children who presented with epilepsy and underwent LEV monotherapy for at least one year (patient group) and 43 healthy children (control group). The CBC parameters (hemoglobin (hb), lymphocytes, leukocytes, neutrophils, and platelets), Ig levels (IgA, IgM, IgG, and IgE), and lymphocyte subsets (CD3, CD4, CD8, CD4/CD8 ratio, CD19, CD56, NKT cells, and Treg cells) were measured and compared between the two groups. The patients were also investigated regarding the frequency and types of infections that they experienced in the first month and first year of the study, and these data were compared between the patient group and the control group. In addition, the same parameters and the frequency of infection were compared among the patient subgroups (focal and generalized seizures). Results: The results of the present study indicate that there were no significant differences in the CBC parameters, lymphocyte subsets, or Ig levels between the patient group and the control group. The comparison among the patient subgroups was similar; however, the CD4/CD8 ratio was lower in the patient subgroup with focal seizures. In addition, there were no significant differences in the frequency or type of infections experienced one month and one year of the study between the patient group and the control group, and likewise for the patient subgroups (focal and generalized seizures). Conclusions: The present study demonstrated that LEV monotherapy did not increase the incidence of infection, and there were no significant effects on the CBC or on the humoral or cellular immune system in epileptic children. These findings also suggest that the CD4/CD8 ratio among lymphocyte subgroups is lower in patients with focal seizures. However, the epilepsy subgroups had a relatively small sample size; therefore, further prospective studies involving a larger patient population are needed to establish the association between LEV monotherapy and lymphocyte subgroups in patients with epilepsy. Full article

Regional HIV-1 epidemics are evolving with distinct patterns in transmission routes, subtype distribution, and molecular transmission cluster (MTCs) characteristics. We analyzed 9500 HIV-1 cases diagnosed over 30 years using phylogenetic and network methods, integrating molecular, epidemiological, demographic, and behavioral data. Subtype A6 remains dominant nationally (80.6%), followed by 63_02A6 (7.9%), subtype B (5.6%), 02_AG_FSU (1.2%), 03_A6B (0.7%), and 14/73_BG (0.6%). Non-A6 infections were more common among males (OR 1.51) and men who have sex with men (OR 7.33). Network analysis identified 421 MTCs, with 256 active clusters. Clustering was more likely among young individuals (OR: 1.31), those not receiving antiretroviral therapy (OR: 2.70), and injecting drug users (OR: 1.28). Non-A6 subtypes showed a higher likelihood of clustering. Phylogenetic analysis revealed that local clusters of the major subtypes originated between the late 1970s (subtype B) and the mid-2000s (63_02A6) with links to populations in Eastern Europe, Central Asia (subtypes A6, 63_02A6, 02_AG_FSU, 03_A6B), and Western Europe and the Americas (subtype B, 14/73_BG). These findings indicate a complex, evolving regional epidemic transitioning from subtype A6 dominance to a more diverse mix of subtypes. The ability of non-A6 subtypes to form active MTCs suggests their establishment in the local population. Full article

The natural history of focal non-infected lesions of the abdominal aorta (fl-AA) remains unclear and largely depends on their aetiology. These lesions often involve a focal “tear” or partial disruption of the arterial wall. Penetrating aortic ulcers (PAUs) and intramural hematomas (IMHs) are examples of focal tears in the aortic wall that can either progress to dilatation (saccular aneurysm) or fail to fully propagate through the medial layers, potentially leading to aortic dissection. These conditions typically exhibit a morphology consistent with eccentric saccular aneurysms. The management of focal non-infected pathologies of the abdominal aorta remains a subject of debate. Unlike fusiform abdominal aortic aneurysms, the inconsistent definitions and limited information regarding the natural history of saccular aneurysms (sa-AAAs) have prevented the establishment of universally accepted practice guidelines for their management. As emphasized in the latest 2024 ESVS guidelines, the focal nature of these diseases makes them ideal candidates for endovascular repair (class of evidence IIa—level C). Moreover, the Society for Vascular Surgery just referred to aneurysm diameter as an indication for treatment suggesting using a smaller diameter compared to fusiform aneurysms. Consequently, the management of saccular aneurysms is likely heterogeneous amongst different centres and different operators. Endovascular repair using tube stent grafts offers benefits like reduced recovery times but carries risks of migration and endoleak due to graft rigidity. These complications can influence long-term success. In this context, the use of endovascular bifurcated grafts may provide a more effective solution for treating these focal aortic pathologies. It is essential to achieve optimal sealing regions through anatomical studies of aortic morphology. Additionally, understanding the anatomical characteristics of focal lesions in challenging necks or para-visceral locations is indeed crucial in device choice. Off-the-shelf devices are favoured for their time and cost efficiency, but new endovascular technologies like fenestrated endovascular aneurysm repair (FEVAR) and custom-made devices enhance treatment success and patient safety. These innovations provide stent grafts in various lengths and diameters, accommodating different aortic anatomies and reducing the risk of type III endoleaks. Although complicated PAUs and focal saccular aneurysms rarely arise in the para-visceral aorta, the consequences of rupture in this segment might be extremely severe. Experience borrowed from complex abdominal and thoracoabdominal aneurysm repair demonstrates that fenestrated and branched devices can be deployed safely when anatomical criteria are respected. Elective patients derive the greatest benefit from a fenestrated graft, while urgent cases can be treated confidently with off-the-shelf multibranch systems, reserving other types of repairs for emergent or bail-out cases. While early outcomes of these interventions are promising, it is crucial to acknowledge that limited aortic coverage can still impede effective symptom relief and lead to complications such as aneurysm expansion or rupture. Therefore, further long-term studies are essential to consolidate the technical results and evaluate the durability of various graft options. Full article

Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific funding bodies. Biofilm formation is regulated by quorum sensing (QS), a population density-dependent communication mechanism between cells mediated by small diffusible signaling molecules. QS modulates various intracellular processes, and some features of QS are common to all Gram-negative bacteria. While there are differences in the QS regulatory networks of different Gram-negative bacterial species, a common feature of most Gram-negative bacteria is the ability of N-acylhomoserine lactones (AHL) as inducers to diffuse across the bacterial membrane and interact with receptors located either in the cytoplasm or on the inner membrane. Targeting QS by inhibiting the synthesis, transport, or perception of signaling molecules using small molecules, quorum quenching enzymes, antibodies, combinatorial therapies, or nanoparticles is a promising strategy to combat virulence. In-depth knowledge of biofilm biology, antibiotic susceptibility, and penetration mechanisms, as well as a deep understanding of anti-QS agents, will contribute to the development of antimicrobial therapies to combat biofilm infections. Advancing antimicrobial therapies against biofilm infections requires a deep understanding of biofilm biology, antibiotic susceptibility, penetration mechanisms, and anti-QS strategies. This can be achieved through in vivo and clinical studies, supported by state-of-the-art tools such as machine learning and artificial intelligence. Full article

Infectious diseases remain a leading cause of mortality worldwide. The pathogenesis that comprises infection, focal inflammation, and immuno-response, typically occurs in one or multiple organs or tissues. Analysis of the molecular composition of affected tissues with their spatial context is pivotal to elucidate the underlying disease mechanisms and to develop accurate diagnostic strategies. In recent years, mass spectrometry imaging (MSI) technology has achieved significant advancements and has emerged as an powerful tool for tissue-based molecular exploration with high molecular specificity and spatial resolution. Although MSI has been rapidly adopted in numerous branches of biomedical research, its application in the field of infectious diseases research is still in its early stages. With this in mind, this review aims to familiarize infectious disease researchers with the advantages and diverse applications of MSI. Additionally, we delineate several existing technical challenges, application pitfalls, and the potential solutions to overcome these challenges. Full article

Vaccination remains the most cost-effective way to control clinical paratuberculosis in dairy herds, but its effect on the immune response at the intestine have been poorly characterized. The aim of this study was to evaluate the expression of toll-like receptor (TLR)-1, TLR2, TLR4, TLR9, interferon (IFN)-γ, inducible nitric oxide synthase (iNOS) and cluster of differentiation (CD)-204 in calves vaccinated with Silirum^® and then experimentally infected with paratuberculosis, using immunohistochemical techniques. Samples of the injection-site granuloma, scapular lymph node, intestine and mesenteric lymph nodes were studied. Lesions were classified as focal, multifocal and diffuse paucibacillary (lymphocytic). The immunolabeling for TLR1, TLR2, TLR4 and IFN-γ was assessed according to the number of immunolabeled cells, while TLR9, iNOS and CD204 immunolabeling in the lesions was evaluated using a histological score (H-score). Vaccinated calves with focal forms showed a significant increase in the number of macrophages immunolabeled TLR2 at the intestine and in the H-score values for iNOS in the granulomas. A greater immunolabeling of TLR2 and IFN-γ was detected at the injection-site granuloma. Animals with multifocal lesions, regardless of the vaccination status, showed lower numbers of TLR2+ macrophages and higher H-score values for CD204 in the granulomas. Thus, the protection conferred by the Silirum^® vaccine is associated with an enhanced immunological response in the intestine. Full article

The Kaliningrad Oblast, located in the westernmost part of Russia and bordering European Union countries, is a popular tourist destination. However, limited research has been conducted on the bacteria found in ticks in this region. We, therefore, investigated the prevalence of certain bacteria, including Borrelia, Rickettsia, Anaplasma, and Ehrlichia, as well as the genospecies of the spotted fever group Rickettsia (SFGR) in Ixodes ricinus and Dermacentor reticulatus tick species. To accomplish this, we employed commercial qPCR for pathogen screening. We identified specific genospecies by sequencing the gltA and ompA gene fragments. In I. ricinus ticks, we found Borrelia burgdorferi sensu lato DNA in 35.6% of samples. We also found Rickettsia helvetica in 17.5% of ticks. Additionally, we detected Borrelia miyamotoi in 1.7% and Anaplasma phagocytophilum in 2.6%, while Ehrlichia chaffeensis/Ehrlichia muris were present in 0.6%. In D. reticulatus ticks, we detected only Rickettsia conorii subsp. raoultii DNA, with a prevalence of 6.1%. These findings demonstrate a substantial risk of Lyme disease and other tick-borne infections from early spring through late autumn, emphasizing the importance of ongoing monitoring for these pathogens in the region. Full article

Murine leukemia viruses (MuLVs) are retroviruses that cause various diseases in mice and have served as a model for retrovirus replication and pathogenesis. MuLVs are separated into infectious exogenous retroviruses (XRVs) and endogenous retroviruses (ERVs) that are remnants of ancient infectious XRVs. Detection of XRVs in the original host cells has some difficulties because of the high similarity in sequence between ERVs and XRVs and expression of some ERV genes. There are some techniques available for monitoring retroviral replication, but each comes with limitations in terms of labor intensity, detection range, cost, and phases after infection. This study developed a novel quantitative PCR (qPCR) method for assessing replication of Moloney MuLV (M-MuLV) in mouse cells. The method amplified the region in packaging signal and gag and distinguished exogenous M-MuLV from ERVs with mouse SC-1 cells. The qPCR system could quantify viral sequences in infected cells from 16 to 72 h post-infection, with a 3-log range of difference. This was compared with the traditional infectivity assay, focal immunofluorescence assay. In conclusion, the developed qPCR system provides a rapid, sensitive, and scalable alternative for quantifying M-MuLV infectivity, with potential for broader applications in MuLV research. Full article

Pine Wilt Disease (PWD) is a highly infectious and lethal disease that severely threatens global pine forest ecosystems and forestry economies. Early and accurate detection of infected trees is crucial to prevent large-scale outbreaks and support timely forest management. However, existing remote sensing-based detection models often struggle with performance degradation in complex environments, as well as a trade-off between detection accuracy and real-time efficiency. To address these challenges, we propose an improved object detection model, YOLOv8-MFD, designed for accurate and efficient detection of PWD-infected trees from UAV imagery. The model incorporates a MobileViT-based backbone that fuses convolutional neural networks with Transformer-based global modeling to enhance feature representation under complex forest backgrounds. To further improve robustness and precision, we integrate a Focal Modulation mechanism to suppress environmental interference and adopt a Dynamic Head to strengthen multi-scale object perception and adaptive feature fusion. Experimental results on a UAV-based forest dataset demonstrate that YOLOv8-MFD achieves a precision of 92.5%, a recall of 84.7%, an F1-score of 88.4%, and a mAP@0.5 of 88.2%. Compared to baseline models such as YOLOv8 and YOLOv10, our method achieves higher accuracy while maintaining acceptable computational cost (11.8 GFLOPs) and a compact model size (10.2 MB). Its inference speed is moderate and still suitable for real-time deployment. Overall, the proposed method offers a reliable solution for early-stage PWD monitoring across large forested areas, enabling more timely disease intervention and resource protection. Furthermore, its generalizable architecture holds promise for broader applications in forest health monitoring and agricultural disease detection. Full article

The opportunistic bacteria Serratia proteamaculans are able to penetrate human cells. It was previously shown that the bacterial surface protein OmpX promotes bacterial adhesion. In addition, infection with bacteria that synthesize the OmpX protein enhances the expression of EGFR and β1 integrin involved in the invasion of S. proteamaculans. Therefore, this work was aimed at determining the mechanism of interaction of S. proteamaculans with receptors of eukaryotic cells. Both integrin-linked kinase (ILK) and EGFR tyrosine kinase have been shown to be involved in the invasion of these bacteria. During infection, EGFR is first phosphorylated at Tyr845, which is carried out by c-Src kinase transmitting a signal from nearby receptors. The S. proteamaculans invasion depends on c-Src and focal adhesion kinase (FAK), which can both transmit a signal between β1 integrin and EGFR and participate in cytoskeletal rearrangements. These bacteria have been shown to interact with integrin not through the RGD binding site, and integrin binding to the RGD peptide enhances adhesion, invasion, and expression of α5 and β1 integrin subunits in response to infection. On the other hand, bacterial adhesion and increased expression of integrins during infection are caused by OmpX. Thus, OmpX interacts with integrins, and the participation of the α5 and β1 integrin subunits in the S. proteamaculans invasion allows us to assume that the receptor of OmpX is α5β1 integrin. Full article

Kidney transplantation is the most effective replacement therapy for kidney failure, providing the best outcomes in terms of patient survival and offering a better quality of life. However, despite the progressive improvement in kidney survival, the recurrence of original disease remains one of the most important causes of graft loss and a major challenge that requires clinical vigilance throughout the transplant’s duration. Additionally, the type and severity of recurrence affect both treatment options and graft survival. This is especially true for the recurrence of systemic diseases. In this narrative review, we will discuss the timing, frequency, severity, and treatment of post-transplant recurrence in three systemic diseases: lupus nephritis (LN), Antineutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (ANCA-GN), and Henoch–Schönlein purpura (HSP). The recurrence of lupus nephritis is less common than that of primary focal segmental glomerulosclerosis or C3 glomerulopathy. Its severity can range from mild mesangial to diffuse proliferative forms, with varying prognoses and treatment options, much like the original disease. In some patients with LN, as well as in those with ANCA-GN or HSP, the reactivation of the primary disease can affect other organs besides the kidneys, potentially leading to life-threatening conditions. These cases may require a multidisciplinary approach, making these transplants clinically more challenging. Extrarenal flare-ups often necessitate an increase in immunosuppression, which in turn raises the risk of infections. In these autoimmune diseases, the role of immunological tests in determining the timing of kidney transplants remains a topic of ongoing debate. However, elevated levels of certain immunological markers, such as anti-dsDNA antibodies, ANCA titers, or serum immunoglobulin A may indicate a reactivation of the disease, suggesting the need for more intensive patient monitoring. Full article

The large yellow croaker (Larimichthys crocea), one of the most economically valuable marine fish species in China, suffers significant economic losses in aquaculture due to infectious diseases caused by marine pathogens, such as Nocardia seriolae. The pathogenic mechanisms underlying N. seriolae infection in L. crocea and the host immune responses remain inadequately characterized. To investigate the molecular mechanisms of this infection, we conducted transcriptome sequencing on the head kidney tissues of L. crocea at 1, 3, 7, and 14 days post-infection with N. seriolae. In total, 421, 1052, 3215, and 2459 upregulated genes, along with 1853, 1777, 3718, and 3134 downregulated genes were identified, respectively. KEGG enrichment analysis revealed that differentially expressed genes were predominantly associated with immune and metabolic pathways. Notably, pathways involved in Toll-like receptor signaling, ECM–receptor interaction, cytokine–cytokine receptor interaction, and focal adhesion were significantly enriched, highlighting an immune response to N. seriolae infection in L. crocea. In addition, significant enrichment of the citrate cycle (TCA cycle) and oxidative phosphorylation pathways in metabolic processes suggests an upregulated ATP synthesis to meet the heightened energy demand associated with the immune response to infection. These findings contribute to a deeper understanding of the immune defense mechanisms in the head kidney of L. crocea against N. seriolae infection and elucidate aspects of N. seriolae pathogenicity. Full article