Search Results (3,219)

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infections (ALRIs) in young children, especially bronchiolitis, with significant global health and economic impact. Increasing evidence links early-life RSV infection to long-term respiratory complications, notably recurrent wheezing and asthma. This narrative review examines these associations, emphasizing predictive factors and emerging biomarkers for risk stratification. Early RSV infection can trigger persistent airway inflammation and immune dysregulation, increasing the likelihood of chronic respiratory outcomes. Risk factors include severity of the initial infection, age at exposure, genetic susceptibility, prematurity, air pollution, and tobacco smoke. Biomarkers such as cytokines and chemokines are showing promise in identifying children at higher risk, potentially guiding early interventions. RSV-related bronchiolitis may also induce airway remodeling and promote Th2/Th17-skewed immune responses, mechanisms closely linked to asthma development. Advances in molecular profiling are shedding light on these pathways, suggesting novel targets for early therapeutic strategies. Furthermore, passive immunization and maternal vaccination offer promising approaches to reducing both acute and long-term RSV-related morbidity. A deeper understanding of RSV’s prolonged impact is essential to develop targeted prevention, enhance risk prediction, and improve long-term respiratory health in children. Future studies should aim to validate biomarkers and refine immunoprophylactic strategies. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multifactorial disorder driven by a combination of disruptions in proteostasis and organelle communication. The 2020 Lancet commission reported that approximately 10 million people worldwide were affected by AD in the mid-20th century. AD is the most prevalent cause of dementia. By early 2030, the global cost of dementia is projected to rise by USD 2 trillion per year, with up to 85% of that cost attributed to daily patient care. Several factors have been implicated in the progression of neurodegeneration, including increased oxidative stress, the accumulation of misfolded proteins, the formation of amyloid plaques and aggregates, the unfolded protein response (UPR), and mitochondrial–endoplasmic reticulum (ER) calcium homeostasis. However, the exact triggers that initiate these pathological processes remain unclear, in part because clinical symptoms often emerge gradually and subtly, complicating early diagnosis. Among the early hallmarks of neurodegeneration, elevated levels of reactive oxygen species (ROS) and the buildup of misfolded proteins are believed to play pivotal roles in disrupting proteostasis, leading to cognitive deficits and neuronal cell death. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles is a characteristic feature of AD. These features contribute to chronic neuroinflammation, which is marked by the release of pro-inflammatory cytokines and chemokines that exacerbate oxidative stress. Given these interconnected mechanisms, targeting stress-related signaling pathways, such as oxidative stress (ROS) generated in the mitochondria and ER, ER stress, UPR, and cytosolic chaperones, represents a promising strategy for therapeutic intervention. This review focuses on the relationship between stress chaperone responses and organelle function, particularly the interaction between mitochondria and the ER, in the development of new therapies for AD and related neurodegenerative disorders. Full article

The 13th International Foamy Virus (FV) Conference was held from 8 to 10 November 2023 at the BioParque/Zoological Garden in Rio de Janeiro, Brazil. This was the first conference on spumaretroviruses to be held in the Southern Hemisphere and in the unique environment of the rainforest. New developments and current perspectives in FV research were presented. Highlights of the conference included the structural biology of the envelope protein (Env) and insights into its function and evolution, epidemiologic identification of Amazonian indigenous people with a high prevalence of simian FV (SFV) infections, investigations of virus biology and genomics using synthetic FV DNAs, studies of humoral immune response, and development and applications of SFV vectors. The last day of the meeting was a special tour of the Centro de Primatologia do Rio de Janeiro, located northeast of Rio de Janeiro amidst the protected rainforest, where New World primate hosts of spumaretroviruses are rescued and studied. Our report summarizes the meeting highlights and outcomes for future discussions. Full article

Pyridoxine-dependent epilepsy (PDE) represents a group of rare developmental and epileptic encephalopathies. The most common PDE is caused by biallelic pathogenic variants in ALDH7A1 (PDE-ALDH7A1; OMIM #266100), which encodes α-aminoadipate semialdehyde (α-AASA) dehydrogenase, a key enzyme in lysine catabolism. Affected individuals present with seizures unresponsive to conventional anticonvulsant medications but responsive to high-dose of pyridoxine (vitamin B6). Adjunctive lysine restriction and arginine supplementation have also shown potential in improving neurodevelopmental outcomes. Given the significant benefit of early intervention, PDE-ALDH7A1 is a strong candidate for newborn screening (NBS). However, traditional biomarkers are biochemically unstable at room temperature (α-AASA and piperideine-6-carboxylate) or lack sufficient specificity (pipecolate), limiting their utility for biomarker-based NBS. The recent identification of two novel and stable biomarkers, 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylate (2-OPP) and 6-oxo-pipecolate (oxo-PIP), offers renewed potential for biochemical NBS. We evaluated the feasibility of incorporating 2-OPP, oxo-PIP, and pipecolate into routine butylated FIA-MS/MS workflows used for biochemical NBS. A total of 9402 dried blood spots (DBS), including nine confirmed PDE-ALDH7A1 patients and 9393 anonymized controls were analyzed using a single multiplex assay. 2-OPP emerged as the most sensitive biomarker, identifying all PDE-ALDH7A1 patients with 100% sensitivity and a positive predictive value (PPV) of 18.4% using a threshold above the 99.5th percentile. Combining elevated 2-OPP (above the 99.5th percentile) with either pipecolate or oxo-PIP (above the 85.0th percentile) as secondary marker detected within the same multiplex FIA-MS/MS assay further improved the PPVs to 60% and 45%, respectively, while maintaining compatibility with butanol-derivatized method. Notably, increasing the 2-OPP threshold above the 99.89th percentile, in combination with either pipecolate or oxo-PIP above the 85.0th percentile resulted in both 100% sensitivity and 100% PPV. This study supports the strong potential of 2-OPP-based neonatal screening for PDE-ALDH7A1 within existing NBS infrastructures. The ability to multiplex 2-OPP, pipecolate and oxo-PIP within a single assay offers a robust, practical, high-throughput and cost-effective approach. These results support the inclusion of PDE-ALDH7A1 in existing biochemical NBS panels. Further prospective studies in larger cohorts are needed to refine cutoffs and confirm clinical performance. Full article

While rainfall occurs for several reasons, climate change and urbanization influence its frequency and geographical disparities. Although recent research suggests that urbanization may lead to increased rainfall, insights into how urbanization can trigger rainfall remain limited. We selected the Dallas–Fort Worth (DFW) metroplex, which has minimal orographic and coastal influences, to analyze the urban impact on rainfall. DFW was divided into 256 equal grids (10 km × 10 km) and grouped into four clusters using K-means clustering based on the urbanization ratio. Using Multi-Sensor Precipitation Estimator data (with a spatial resolution of 4 km), we examined rainfall exceeding the 95th percentile (i.e., extreme rainfall) on low synoptic days to highlight localized effects. The urban heat island (UHI) effect was estimated based on the average temperature difference between the urban core and the other three non-urban clusters. Multiple rainfall events were monitored on an hourly basis. Potential linkages between urbanization, the UHI, extreme rainfall, wind speed, wind direction, convective inhibition, and convective available potential energy were evaluated. An intense UHI within the DFW area triggered a tornado, resulting in maximum rainfall in the urban core area under high wind speeds and a dominant wind direction. Our findings further clarify the role of urbanization in generating extreme rainfall events, which is essential for developing better policies for urban planning in response to intensifying extreme events due to climate change. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Background. Medulloblastoma (MB) prognosis and response to therapy depend largely on genetic changes in tumor cells. Many genes and chromosomal abnormalities have been identified as prognostic factors, including amplification of MYC oncogenes, gains in 1q and 17q, deletions in 10q and 21p, or isochromosomes 17 (i(17)(q10)). The frequency of these abnormalities varies greatly between ethnic populations, but the frequency of specific abnormalities, such as MYCC and MYCN amplification, 17q gain, and deletions, in the Russian population is unknown. Objective: The aim is to study the frequency of MYCC and MYCN amplifications, 17q gain, and 17p deletion and determine their prognostic value in Russian patients with MB. Methods. This study was performed on MB cells obtained from 18 patients (12 boys and 6 girls, aged between 3 months and 17 years, with a median age of 6.5 years). Determination of cytogenetic aberrations was carried out using FISH assays with MYCC-SO, MYCN-SO, and MYCN-SG/cen2 probes, as well as cen7/p53 dual color probes and PML/RARα dual color probes (Abbott Molecular, USA). One-way ANOVA and Fisher’s F-test were used to compare the two groups. The differences were considered significant when p < 0.05. Results. In 77.7% of patients (14/18), the classical type of MB was present; in 16.7% (3/18), desmoplastic type; and in 5.6% (1/18), nodular desmoplasic types of neoplasms. Amplification of MYC genes was detected in 22.2% of Russian patients (n = 4 out of 18). Patients with MYC amplification had the worst overall survival (OS: 0% vs. 68%, p = 0.0004). Changes on the 17th chromosome were found in 58.3% of patients. Deletion of 17p occurred in 23.1%, and gain of 17q occurred in 46.2%. There were no significant differences in OS, clinical signs, or the presence of additional 17q material or 17p deletion among patients with MB. Conclusions: Amplification of the MYC gene is a predictor of poor overall survival to therapy and a high risk of metastatic relapse. This allows us to more accurately stratify patients into risk groups in order to determine the intensity and duration of therapy. Full article

Background/Objectives: The Pleth Variability Index (PVI) is a non-invasive parameter used to guide fluid management by reflecting respiratory-induced variations in the plethysmographic waveform. While PVI’s reliability in various positions has been studied, data on its behavior in geriatric patients undergoing transurethral resection of the prostate (TUR-P) in the lithotomy position remain limited. This study aimed to evaluate the effect of the lithotomy position on PVI in geriatric versus non-geriatric patients under spinal anesthesia. Methods: This prospective observational study included 90 patients undergoing elective TUR-P in the lithotomy position under spinal anesthesia. Patients were divided into geriatric (≥65 years, n = 48) and non-geriatric (<65 years, n = 42) groups. PVI and Perfusion Index (PI) were recorded at baseline, in the supine position, and in the lithotomy position. Fluid and vasopressor requirements, along with hemodynamic parameters, were also analyzed. Results: PVI values at the 5th minute in the lithotomy position were significantly higher in the geriatric group compared to the non-geriatric group (p = 0.019). No significant differences were observed in PI values or intraoperative hypotension rates between the groups. Neurological comorbidities were more prevalent in the geriatric group (p = 0.025). Conclusions: PVI appears to be a more sensitive indicator of fluid responsiveness in elderly patients under spinal anesthesia in the lithotomy position. Its age-dependent variability suggests clinical utility in guiding fluid management in geriatric populations, while the stable hypotension rates support the effectiveness of PVI-guided goal-directed therapy. Full article

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

Vaccine adjuvants are non-immunogenic agents that enhance or modulate immune responses to co-administered antigens and are essential to modern vaccines. Despite their importance, few are approved for human use. The rise of new pathogens and limited efficacy of some existing vaccines underscore the need for more advanced and effective formulations, particularly for vulnerable populations. Aluminum-based adjuvants are commonly used in vaccines and effectively promote humoral immunity. However, they mainly induce a Th2-biased response, making them suboptimal for diseases requiring cell-mediated immunity. In contrast, saponin-based adjuvants from the Quillajaceae family elicit a more balanced Th1/Th2 response and generate antigen-specific cytotoxic T cells (CTL). Due to ecological damage and limited availability caused by overharvesting Quillaja saponaria Molina barks, efforts have intensified to identify alternative plant-derived saponins with enhanced efficacy and lower toxicity. Quillaja brasiliensis (A.St.-Hil. and Tul.) Mart. (syn. Quillaja lancifolia D.Don), a related species native to South America, is considered a promising renewable source of Quillajaceae saponins. In this review, we highlight recent advances in vaccine adjuvant research, with a particular focus on saponins extracted from Q. brasiliensis leaves as a sustainable alternative to Q. saponaria saponins. These saponin fractions are structurally and functionally comparable, exhibiting similar adjuvant activity when they were formulated with different viral antigens. An alternative application involves formulating saponins into nanoparticles known as ISCOMs (immune-stimulating complexes) or ISCOM-matrices. These formulations significantly reduce hemolytic activity while preserving strong immunoadjuvant properties. Therefore, research advances using saponin-based adjuvants (SBA) derived from Q. brasiliensis and their incorporation into new vaccine platforms may represent a viable and sustainable solution for the development of more less reactogenic, safer, and effective vaccines, especially for diseases that require a robust cellular immunity. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants. Full article

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

The enhancement of flavonoid content and antioxidant capacity in plants remains a significant area of focus in the investigation of plant-derived functional foods. This study systematically investigated the impact of exogenous zinc sulfate (5 mM ZnSO₄) stress on flavonoid content and antioxidant capacity in finger millet (Eleusine coracana L.) sprouts, along with its underlying molecular mechanisms. The results demonstrated that treatment with 5 mM ZnSO₄ significantly increased the flavonoid content in sprouts, reaching a maximum value of 5.59 μg/sprout on the 6th day of germination. ZnSO₄ stress significantly enhanced the activities of PAL, 4CL, and C4H, while also considerably upregulating the expression levels of flavonoid-biosynthesis-related genes. Physiological indicators revealed that ZnSO₄ stress increased the contents of malondialdehyde, hydrogen peroxide, and superoxide anion in the sprouts, while inhibiting sprout growth. As a stress response, ZnSO₄ stress enhances the antioxidant system by increasing antioxidant capacity (ABTS, DPPH, and FRAP), antioxidant enzyme activity (POD and SOD), and related gene expression (POD, CAT, and APX) in sprouts. This study provides experimental evidence for ZnSO₄ stress to improve flavonoid accumulation and antioxidant capacity in finger millet sprouts and provides important theoretical and practical guidance for the development of high-quality functional foods. Full article