Search Results (676)

Pigeon paramyxovirus type 1 (PPMV-1) poses a significant threat to pigeon farming in China, and understanding its biological characteristics and pathogenicity is critical for vaccine development and disease control. In this study, we characterized a PPMV-1 QY strain, performed full-length genome sequencing, and constructed a phylogenetic tree based on the F gene. Then, the biological properties and the pathogenicity of the QY strain were assessed and evaluated in vitro and in vivo. The results showed that phylogenetic analysis classified the QY strain within subgenotype VI.2.1.1.2.2, the predominant circulating strain in China. The QY strain exhibited a 50% egg infectious dose (EID₅₀) of 10^−6.8/0.1 mL, mean death time (MDT) in chicken embryos of 68.7 ± 2.1 h, and intracerebral pathogenicity index (ICPI) in one-day-old chicks of 1.12, which indicate it is a moderately virulent strain. Animal experiments showed that the QY strain resulted in a mortality rate of 66.7% in healthy pigeons. Necropsy findings included cerebral congestion and swelling, hemorrhagic glandular stomach papillae, tracheal ring hemorrhages, and duodenal congestion and swelling. Histopathological analysis revealed extensive inflammatory infiltration in the lungs and liver, widespread intestinal erosion, and severe necrosis of splenic red pulp cells. In conclusion, the QY strain belongs to subgenotype VI.2.1.1.2.2 and exhibits moderate virulence, causing high mortality and severe pathological lesions in infected pigeons. These findings provide valuable insights into the pathogenicity of PPMV-1 and the specific mutations in the F protein can serve as potential attenuation targets in vaccine development against the emerging subgenotype VI.2.1.1.2.2. Full article

This article presents the report of the First International Congress of Preventive Medicine, organized by the Romanian Society of Preventive Medicine (SRMP) in March 2025, in Bucharest, Romania. The congress featured 11 discussion panels and workshops, bringing together over 85 experts from a wide range of medical disciplines, including oncology, vaccination, cardiology, endocrinology, gynecology, gastroenterology, surgery, family medicine, physical therapy, pulmonology, epidemiology, pediatrics, dentistry, pathology, ENT, genetics, pediatric cardiology, psychiatry, dermatology, plastic surgery, urology, infectious diseases, regenerative medicine, and other key stakeholders in preventive healthcare. The event served as a comprehensive platform for addressing critical public health challenges, with a focus on cancer prevention, anti-aging, oral health, genetics in preventive medicine, preventive cardiology and neurology, the correlation between craniofacial dysfunctions and posture, vaccination strategies, management of congenital malformations, neonatal screening, and the prevention of lifestyle-related diseases such as obesity and tobacco addiction. Furthermore, the congress highlighted the importance of interdisciplinary collaboration and evidence-based interventions in improving population health outcomes. It emphasized the urgent need for coordinated actions to address preventable diseases both at the national and international levels. Full article

Background/Objectives: Classical swine fever (CSF) is listed by the World Organisation for Animal Health as a highly devastating and contagious pig disease, causing severe economic losses to the swine industry. In spite of the successful elimination of CSF in Taiwan, preparedness against potential reintroduction remains essential. The live attenuated vaccines have been effective in disease control, but are not capable of a viable strategy that differentiates infected from vaccinated animals (DIVA). Subunit vaccines are recognized for their safety and ability to induce protective immunity against infectious diseases. Methods: In this study, the recombinant CSF virus (CSFV) E2 proteins were formulated with a CpG motif as an adjuvant to produce the E2-CpG subunit vaccine. Its efficiency in specific-pathogen-free (SPF) pigs was compared with a commercially available E2 subunit vaccine (Bayovac^® CSF-E2; Bayer Taiwan Co., Ltd., Taipei City, Taiwan). Results: Significantly higher titers of anti-E2 antibodies were induced in pigs immunized with a single dose of the E2-CpG vaccine, particularly the reduced E-0.5A formulation, than those immunized with a dose of the commercialized E2 subunit vaccine adjusted to double dosage. This designed subunit vaccine showed high efficacy in protection against clinical symptoms and significant pathological alterations in pigs after a highly virulent CSFV (genotype 1.1) challenge. Viral shedding was not detected in vaccinated pigs before completion of the challenge study, and the viral load in their spleens remained undetectable. Conclusions: These results could support the potential of the E2-CpG vaccine as a cost-effective, single-dose subunit vaccine capable of inducing robust CSFV-specific immunity and providing 100% protection against lethal CSFV challenges. Full article

The urokinase-type plasminogen activator receptor (uPAR) plays a pivotal role in regulating extracellular proteolysis, cell migration, immune responses, and tissue remodeling across diverse physiological and pathological contexts. This review provides detailed insights into the structure of uPAR, ligand interactions, and signaling mechanisms, emphasizing its central function in cancer progression, including tumor invasion, metastasis, angiogenesis, and modulation of the tumor microenvironment. We also summarize the involvement of uPAR as a key player in cardiovascular, infectious, and neurological diseases, where it contributes to inflammation, tissue damage, and disease progression. However, translational gaps remain, most notably inconsistent assay harmonization (especially for suPAR), uncertain context-specific cut-offs and patient-selection criteria and limited multicenter validation for uPAR-targeted imaging and therapeutics. This review addresses these gaps by synthesizing cross-disease evidence to clarify clinical use cases and outline practical selection frameworks. Furthermore, we discuss the clinical potential of uPAR as a diagnostic and prognostic biomarker in diverse disease contexts, along with recent advances in therapeutic strategies targeting uPAR. Full article

Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation—classical, lectin, and alternative—are implicated in developing cardiac damage, inflammation, and hypertrophy due to infectious and non-infectious causes, autoimmune diseases, genetic polymorphisms, and forms of complement dysregulation. Of interest in this review is the role of the complement system, a collection of soluble and membrane-bound proteins that mediate inflammatory processes through interactions with signaling molecules and immune cells. This review comprehensively discusses the roles of these complement pathways in contagious, chronic inflammatory, genetic, and metabolic diseases. An overview of the completed and terminated clinical trials aimed at preventing cardiovascular mortality by targeting various aspects of the complement system and inflammatory reaction is included. Most current treatments for cardiac inflammation and remodeling primarily target the renin–angiotensin–aldosterone system (RAAS), which prevents further remodeling by reducing myocardial workload. However, moving forward, there may be a place for emerging anti-complement therapeutics, which impair the inflammatory response that generates hypertrophy itself. Full article

Background/Objectives: Sweet’s syndrome (SS), also known as acute febrile neutrophilic dermatosis, is a rare inflammatory skin disorder that may also present with extracutaneous manifestations. Liver involvement is thought to result from sterile neutrophilic infiltration, mirroring the skin pathology and highlighting the syndrome’s systemic inflammatory nature. Timely recognition, exclusion of infectious or autoimmune etiologies, and prompt corticosteroid therapy are critical for favorable outcomes. Methods: Herein, we present the case of a 73-year-old man with hyperuricemia who developed both cutaneous and systemic manifestations of SS seven days after initiating allopurinol treatment. His symptoms included fever, conjunctivitis in the right eye, and painful, non-pruritic erythematous plaques, some with pustules, on the lower limbs, palms, and face. Results: Initial laboratory investigations revealed neutrophilic leukocytosis, elevated inflammatory markers, and renal and hepatic dysfunction. Empirical treatment with antibiotics and antivirals failed to improve his condition. The patient discontinued allopurinol and initiated a high-dose corticosteroid regimen, leading to rapid resolution of fever and improvement in skin lesions. Laboratory parameters gradually normalized, except for persistent high liver enzymes. A comprehensive diagnostic workup ruled out infectious, autoimmune, and malignant causes. Imaging studies, including CT, MRI, and MRCP, showed no structural liver abnormalities. Skin biopsy findings were consistent with SS, demonstrating dense neutrophilic infiltrates in the reticular dermis and papillary dermal edema. After his discharge, he was followed up by the Hepatology unit. The patients’ liver enzyme levels normalized within three months with no recurrence or late complications one year later. Conclusions: In the context of drug-induced SS, persistent hepatic abnormalities, although rare, may occur in patients without underlying liver disease. Full article

Background and Objectives: Diabetic foot gangrene remains a major cause of lower limb amputation, driven by vascular, neuropathic, and infectious mechanisms. Identifying predictors for amputation type is essential to optimizing outcomes and reducing disability. We aimed to analyze the burden of diabetic foot gangrene and the patients’ characteristics according to the type of surgery, minor or major amputations. Methods: We conducted a retrospective observational study including 295 diabetic patients who underwent surgery for foot lesions at a Romanian tertiary center (January 2023–December 2024). Patients were classified according to surgical outcome as minor (toe/foot-level) or major (below/above-knee) amputations. Clinical, demographic, and pathological variables were compared between groups. Statistical analysis was performed with IBM SPSS Statistics 20.0. Categorical variables were expressed as frequencies and percentages, and continuous variables as mean ± SD or median (min–max). Group comparisons used Student’s t-test, Mann–Whitney U, Chi-square, or Fisher’s exact test, and binary logistic regression was applied to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: Among the patients included (mean age 64.8 ± 10.8 years; 69.2% male), 191 (64.7%) underwent minor amputations/debridement and 104 (35.3%) required major amputations. Patients with major amputations were older (66.8 ± 11.3 vs. 63.7 ± 10.4 years, p = 0.012) and less frequently male (56.7% vs. 75.9%, p = 0.001). Lesion extension to the foot or beyond strongly predicted major amputation (p < 0.001). Peripheral arterial disease was more prevalent in the major group (85.6% vs. 65.4%, OR = 3.13, 95% CI = 1.68–5.84), while neuropathy was associated with minor procedures (12.6% vs. 3.8%, p = 0.015). Anemia (70.2% vs. 56.5%, p = 0.021) and leukocytosis (68.3% vs. 49.2%, p = 0.002) were also independent predictors of major amputation. Conclusions: The study highlights the need for early detection, coordinated multidisciplinary care, and personalized assessment of diabetes burden and its complications to minimize the risk of major limb amputation. Full article

The BCL2 family of proteins plays a pivotal role in regulating apoptosis and cellular homeostasis, making them critical therapeutic targets in cancer and other diseases characterized by pathological cell survival. BH3 mimetics, small molecules that selectively inhibit anti-apoptotic BCL2 family members, have achieved significant clinical success, particularly in hematologic malignancies. However, several challenges remain, including resistance mechanisms, toxicity (such as MCL1 inhibitor-associated cardiotoxicity), and the intricate balance between apoptotic and non-apoptotic functions. This review provides a comprehensive overview of BCL2 family biology, the development and clinical application and outcomes of BH3 mimetics, and the emerging resistance mechanism known as double-bolt locking. We also examine strategies to overcome resistance, including combination therapies and immunomodulatory approaches. Beyond oncology, we highlight the expanding therapeutic potential of BH3 mimetics in autoimmune, fibrotic, and infectious diseases, as well as regenerative and anti-aging medicine. Finally, we discuss predictive biomarkers and tissue-specific responses that inform precision therapy. Together, these insights underscore the promise of BH3 mimetics and the need for continued multidisciplinary research to optimize their clinical impact. Full article

Background and Objectives: Infective endocarditis (IE) remains a severe infection with high morbidity and mortality, particularly among people who inject drugs (PWID). Data from Eastern Europe are limited, despite the increasing burden of intravenous drug use in the region. Materials and Methods: We conducted a retrospective, observational cohort study of 153 patients diagnosed with IE and admitted to the “Dr. Victor Babeș” Clinical Hospital for Infectious and Tropical Diseases in Bucharest, Romania, between August 2019 and July 2024. Patients were classified into PWID (n = 51) and non-PWID (n = 102). Clinical characteristics, microbiological profiles, echocardiographic findings, complications, and outcomes (in-hospital, 10-week, and 12-month mortality) were compared between groups. Results: PWID were significantly younger (mean 34.0 ± 6.6 years vs. 64.3 ± 13.1 years; p < 0.001), predominantly male (86.3% vs. 62.7%; p = 0.003) and had higher rates of HIV (64.7%) and HCV (98.1%). Right-sided IE and larger vegetations were more common in PWID, whereas non-PWID had more left-sided disease, pre-existing valvular pathology, and prosthetic valve involvement. Staphylococcus aureus predominated in PWID (68.6% vs. 27.5%; p < 0.001), while non-PWID had more Streptococcus spp. and Coxiella burnetii cases. Embolic complications, particularly pulmonary emboli, and valvular rupture were significantly more frequent in PWID, while non-PWID had higher rates of heart failure and surgical interventions. In-hospital mortality was similar (17.6% vs. 11.8%; p = 0.318), but 12-month mortality was higher in PWID (27.5% vs. 13.7%; p = 0.038). Conclusions: IE in PWID shows a distinct clinical and microbiological profile, with more aggressive complications and worse long-term survival. Tailored management, early diagnosis, harm reduction programs, and dedicated follow-up are urgently needed in this high-risk population. Full article

The monkeypox virus (MPXV) has spread globally, posing a severe challenge to global public health. This study systematically evaluated the aerosol shedding dynamics of the epidemic Clade IIb MPXV strain in infected young rabbits, along with its direct contact and airborne transmission potential among them. We found that young rabbits could be experimentally infected with MPXV, exhibiting distinct pathogenic features and viral shedding patterns. Young rabbits infected with MPXV shed the virus through nasal secretions and exhaled aerosols, peaking at 7 dpi. In total, 89–95.8% of virus-laden respiratory particles had a diameter ≥4.7 μm. Notably, MPXV can be efficiently shed and transferred among young rabbits through direct contact and airborne routes. The nasal secretions and exhaled virus particles from donor rabbits can be contacted or inhaled by recipient rabbits. Large amounts of viral DNA were detected in the nasal wash of rabbits exposed to contact or airborne exposure. Furthermore, virus particles invade the lungs, causing pathological changes and disseminating them to multiple organs. However, no infectious virus was successfully recovered from these recipient rabbits, as their exposed or inhaled MPXV dose might have been below the MPXV’s minimum infectious dose for young rabbits. These findings indicate that although the airborne transmissibility of the current MPXV strain is relatively limited, inhalation of viral particles following airborne exposure can still result in bodily damage. Continuous monitoring of MPXV transmissibility and mutation evolution is imperative to prevent efficient respiratory aerosol transmission, which guides global monkeypox prevention and control strategies. Full article

This study investigated the structural features of adult duck liver and compared pathological alterations induced by duck Tembusu virus (DTMUV, strain XZ-2012) and lipopolysaccharide (LPS). Histological techniques (HE, reticular fiber, and trichrome staining) revealed normal duck liver exhibited reddish-brown coloration with indistinct lobule boundaries and no prominent bile ducts. Kupffer cell distribution was mapped via jugular ink injection. DTMUV infection caused liver swelling, congestion, and yellowish discoloration. Histopathology showed lymphocyte infiltration around central veins and portal areas, increased reticular fibers, thickened basement membranes, hepatocyte vacuolation, and erythrocyte accumulation in sinusoids. In contrast, LPS exposure led to mild hepatic enlargement without vacuolar degeneration but with marked perivascular lymphocyte aggregation and reticular fiber proliferation. Both treatments elevated Kupffer cell numbers. These findings demonstrate distinct liver injury patterns: DTMUV induces direct hepatocellular damage with inflammatory responses, while LPS triggers intense immune cell recruitment without significant hepatocyte degeneration. The study provides insights into avian viral versus bacterial pathogenesis and liver defense mechanisms, offering a foundation for further research into waterfowl infectious diseases. Full article

P-Glycoprotein (P-gp, also known as MDR1 or ABCB1) is an ATP-binding cassette (ABC) transporter that actively effluxes a wide range of structurally and functionally diverse molecules, playing a crucial role in drug absorption, distribution, and excretion. P-gp is highly expressed at key biological barriers, such as the blood–brain barrier (BBB), intestine, liver, and kidneys, and it serves as a gatekeeper against xenobiotics and therapeutics. Its dysregulation is involved in multidrug resistance (MDR), epilepsy, cancer, infectious diseases, and neurodegenerative disorders. Several small molecules were synthesized using SAfIR and SAR, and, among them, [¹⁸F]MC225 showed the most promising results for in vivo human studies, with appropriate pharmacodynamics and pharmacokinetics profiles for in vivo use. [¹⁸F]MC225 is currently being employed in PHASE II human trials at the UMC Groningen, the Netherlands, in patients diagnosed with AD, PD and MCI, as well as PHASE II human trials at the Policlinico Gemelli in Rome Italy to diagnose P-gp resistant depression. Preliminary studies show that [¹⁸F]MC225 radiotracer is behaving according to the initial predictions, that is, it accurately diagnoses the aforementioned pathologies, more so than previously developed small molecules for the same goal. Full article

SARS-CoV-2, the agent responsible for coronavirus disease in 2019 (COVID-19), has caused extensive global health and socioeconomic impact due to its transmissibility and pathology. As a result, it was classified as a Risk Group 3 human pathogen, and handling samples containing live virus requires enhanced biological containment facilities (i.e., CL3) to reduce the potential of laboratory infection to personnel and the spread of the virus into the community. While the use of an authentic live virus remains the gold standard for biological assays, alternative methods have been developed to effectively evaluate neutralization activity in the absence of a replicating viral agent. Here, we describe a cell-based spike–ACE2 binding assay as a surrogate for neutralization of SARS-CoV-2 spike to identify potential neutralizing antibodies. A main advantage of this approach is the exclusion of infectious viral particles, increasing biosafety for laboratory personnel. The interaction of recombinant SARS-CoV-2 trimeric spike protein with ACE2 is monitored and quantified by flow cytometry. Notably, our previous studies have demonstrated the utility of this assay for other viruses, beyond SARS-CoV-2. The methodology presented here has exhibited a strong correlation to other widely accepted methods, such as pseudotyped lentiviral and live virus neutralization assays, in identifying neutralizing antibodies. Full article

The cGAS-STING pathway initiates the core cascade of innate immune defense by recognizing pathogen-associated and self-derived abnormal nucleic acids, and key molecules (such as cGAS, STING, downstream IFN-β, IL-6, etc.) may serve as biomarkers in various diseases. The diverse mechanisms by which distinct nucleic acids activate this pathway provide novel insights for therapeutic strategies targeting infectious diseases, cancer, and autoimmune disorders. To prevent aberrant cGAS-STING pathway activation, cells employ multiple regulatory mechanisms, including restricting self-DNA recognition and terminating downstream signaling. Strategies to mitigate pathological activation involve reducing nucleic acid accumulation through nuclease degradation (e.g., of mitochondrial DNA or neutrophil extracellular traps, NETs) or directly inhibiting cGAS or STING. This review elucidates the molecular mechanism of nucleic acid-mediated regulation of cGAS-STING and its role in disease regulation. Full article

Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 (DNAJC30) c.152A>G p.(Tyr51Cys) founder variant. Case Presentation: A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the DNAJC30 gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient’s condition. Conclusion: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians. Full article