Search Results (22)

Background: Three-finger toxins (3FTxs) are a major axis of functional diversification in advanced snake venoms, with canonical paralytic activity mediated through muscle-type nicotinic acetylcholine receptors (nAChRs) and a broader set of non-nicotinic targets. This review integrates evidence bearing on coevolution between 3FTxs and target receptors, spanning toxin origin, diversification, receptor evolution, and ecological context. Methods: The synthesis draws on comparative genomic and transcriptomic studies of 3FTx gene-family evolution, codon-model analyses of selection, structural characterisation of toxin–receptor interfaces, and functional assays (including receptor-mimicking peptide binding) that link sequence variation to binding and toxicity. Results: Across lineages, 3FTx diversification is repeatedly structured by strong constraint on the disulphide-rich scaffold with accelerated change concentrated in solvent-exposed loops, alongside birth–death dynamics and exon/segment-level innovation that expand binding specificity. On the receptor side, resistance-associated variation is most intensively characterised for the nAChR α₁ orthosteric site and includes convergent, mechanistically distinct solutions such as electrostatic repulsion and glycosylation-mediated steric interference. Within the predominantly elapid systems currently examined, integrative datasets indicate that prey-selective binding and geographically variable susceptibility can arise from modest substitutions at toxin–receptor interfaces, but they also reveal substantial taxonomic and target-specific biases. Conclusions: Current evidence supports adaptive diversification in both toxins and receptors, while broader evolutionary interpretations are limited by uneven sampling and the frequent lack of matched toxin and receptor variants analysed within a common evolutionary framework. Development of predictive models will require joint pipelines linking genomics, structure-informed evolutionary inference, scalable functional assays, and explicit ecological network context. Full article

Background/Objectives: Rheumatic fever is preventable and can be treated successfully; however, a lack of understanding of the disease and barriers to timely healthcare can impact outcomes. Pacific people in Aotearoa New Zealand experience inequitable burdens, and a Pacific community group and health professional network are working together to co-design education initiatives. This descriptive, mixed-methods study aimed to (1) explore Pacific people’s awareness and understanding of rheumatic fever, (2) describe where Pacific people access health information. Methods: An online survey co-developed with Pacific community members was run from December 2024 to February 2025. Questions related to sore throats, rheumatic fever, medication adherence, long-term outcomes and where Pacific people access health information. Quantitative data was analyzed descriptively using SPSS version 28 and open-ended qualitative responses were analyzed using an inductive content analysis approach. Results: A total of 400 Pacific respondents were included: 34% were aged 16–24 years and 66% were female. Based on the analysis, 71% of Pacific participants knew that a sore throat should always be checked by a health professional and 65.3% had heard of rheumatic fever. Fever and sore throats were commonly identified as symptoms of rheumatic fever, with joint pain, body aches and chest pain mentioned less. Barriers to health services such as cost, long waiting times and cultural factors were discussed as reasons why many Pacific people often utilize social media and online forums for health information. Conclusions: This study highlights gaps in rheumatic fever knowledge and thus opportunities for health education initiatives for Pacific communities, potentially utilizing social media and online platforms. Full article

The risk of developing symptomatic knee osteoarthritis (KOA) during a lifetime, i.e., pain, aching, or stiffness in a joint associated with radiographic KOA, was estimated in 2008 to be around 40% in men and 47% in women. The clinical and scientific communities lack an efficient diagnostic method to effectively monitor, evaluate, and predict the evolution of KOA before and during the therapeutic protocol. In this review, we summarize the main methods that are used or seem promising for the diagnosis of osteoarthritis, with a specific focus on non- or low-invasive methods. As standard diagnostic tools, arthroscopy, magnetic resonance imaging (MRI), and X-ray radiography provide spatial and direct visualization of the joint. However, discrepancies between findings and patient feelings often occur, indicating a lack of correlation between current imaging methods and clinical symptoms. Alternative strategies are in development, including the analysis of biochemical markers or acoustic emission recordings. These methods have undergone deep development and propose, with non- or minimally invasive procedures, to obtain data on tissue condition. However, they present some drawbacks, such as possible interference or the lack of direct visualization of the tissue. Other original methods show strong potential in the field of KOA monitoring, such as electrical bioimpedance or near-infrared spectrometry. These methods could permit us to obtain cheap, portable, and non-invasive data on joint tissue health, while they still need strong implementation to be validated. Also, the use of Artificial Intelligence (AI) in the diagnosis seems essential to effectively develop and validate predictive models for KOA evolution, provided that a large and robust database is available. This would offer a powerful tool for researchers and clinicians to improve therapeutic strategies while permitting an anticipated adaptation of the clinical protocols, moving toward reliable and personalized medicine. Full article

Topical formulations that include natural active compounds to treat inflamed and aching skin are favored by patients. Small local producers use commercial creams and gels to which they add compounds, often with criteria based more on trends than scientific evidence, to obtain products to treat inflamed joints or skin. Based on our previous studies that demonstrated the anti-inflammatory and analgesic effects of Harpagophytum procumbens extracts and N-acetylglucosamine, we were interested in preparing formulations with these natural substances for topical applications. In the present study, we compared the rheological properties of various creams and gels with bulk and nanoparticle forms of N-acetylglucosamine added, focusing on the flow properties of multiphase emulsion. Moreover, the ability of nanoparticles to reduce inflammation and stimulate collagen production was demonstrated in both chondrocyte and fibroblast spheroids. The results showed the activity of nano-N-acetylglucosamine in our cell models, suggesting its suitability for use as a component in creams and gels. Furthermore, its ability to affect the flow properties of commercial creams and gels makes it an ideal component of topical formulations for the treatment of inflamed skin and joints. Full article

To obtain the Passivhaus Certificate or Passivhaus Standard (PHS), requirements regarding building envelope air tightness must be met: according to the n₅₀ parameter, at a pressure of 50 Pa, air leakage must be below 0.6 air changes per hour (ACH). This condition is verified by following the blower door test protocol and is regulated by the ISO 9972 standard, or UNE-EN-13829. Some construction techniques make it easier to comply with these regulations, and in most cases, construction joints and material joints must be sealed in a complex way, both on façades and roofs and at ground contact points. Performing rigorous quality control of these processes during the construction phase allows achieving a value below 0.6 ACH and obtaining the PHS certification. Yet, the value can increase substantially with the passage of time: as windows and doors are used, opened, or closed; as envelope materials expand; with humidity; etc. This could result in significant energy consumption increases and losing the PHS when selling the house at a later point in time. It is therefore important to carefully supervise the quality of the construction and its execution. In this study, we focused on a house located in Sitges (Barcelona). The envelope air tightness quality was measured during four construction phases, together with the sealing of the joints and service ducts. The blower door test was performed in each phase, and the n₅₀ value obtained decreased each time. The execution costs of each phase were also determined, as were the investment amortisation rates based on the consequent annual energy demand reductions. Air infiltration dropped by 43.81%, with the final n₅₀ value resulting in 0.59 ACH. However, the execution costs—EUR 3827—were high compared to the energy savings made, and the investment amortisation period rose to a 15- to 30-year range. To conclude, these airtightness improvements are necessary in cold continental climates but are not applicable on the Spanish Mediterranean coast. Full article

Post-COVID syndrome, also known as long COVID, includes a range of symptoms that persist for months or even years after initial infection such as fatigue, shortness of breath, joint pain, chest pain, muscle aches, and heart palpitations, among others. In addition, long COVID is related with new-onset diseases such as diabetes mellitus. The association between SARS-CoV-2 infections and the development of diabetes mellitus is complex and not fully understood. Therefore, the objective of this article was to summarize the state of the art in possible mechanisms involved in the development of diabetes mellitus in the post-COVID-19 era, particularly the impact of SARS-CoV-2 variants on molecular mimicry, the role of viral m6A RNA methylation, and the potential associations between these factors. A better understanding of the combinatorial effects of these mechanisms is paramount for both clinicians and researchers alike because it could help tailor more effective treatment strategies, enhance patient care, and guide future research efforts. Full article

Lead (Pb) and arsenic (As) are commonly occurring heavy metals in the environment and produce detrimental impacts on the central nervous system. Although they have both been indicated to exhibit neurotoxic properties, it is not known if they have joint effects, and their mechanisms of action are likewise unknown. In this study, zebrafish were exposed to different concentrations of Pb (40 μg/L, 4 mg/L), As (32 μg/L, 3.2 mg/L) and their combinations (40 μg/L + 32 μg/L, 4 mg/L + 3.2 mg/L) for 30 days. The histopathological analyses showed significant brain damage characterized by glial scar formation and ventricular enlargement in all exposed groups. In addition, either Pb or As staining inhibited the swimming speed of zebrafish, which was enhanced by their high concentrations in a mixture. To elucidate the underlying mechanisms, we examined changes in acetylcholinesterase (AChE) activity, neurotransmitter (dopamine, 5-hydroxytryptamine) levels, HPI axis-related hormone (cortisol and epinephrine) contents and neurodevelopment-related gene expression in zebrafish brain. The observations suggest that combined exposure to Pb and As can cause abnormalities in swimming behavior and ultimately exacerbate neurotoxicity in zebrafish by interfering with the cholinergic system, dopamine and 5-hydroxytryptamine signaling, HPI axis function as well as neuronal development. This study provides an important theoretical basis for the mixed exposure of heavy metals and their toxicity to aquatic organisms. Full article

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR⁺ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR⁺ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR⁺ and IL-17A⁺ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR⁺IL-17A⁺ and α7 nAChR⁺IL-17A⁺FOXP3⁺ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR⁺ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR⁺ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice. Full article

Vaccination programs in the first years of a child’s life are effective and extremely important strategies for the successful eradication of diseases. However, as no intervention is without risks, the metal-based components of some vaccines, such as thimerosal (TMS), a preservative composed of ethylmercury, and aluminum (Al), have begun to generate distrust on the part of the population. Therefore, this study evaluated the effects of exposure to thimerosal and aluminum hydroxide (alone or in mixture) on Danio rerio (zebrafish) specimens. The fish were exposed to thimerosal and/or aluminum hydroxide intraperitoneally. The liver, kidney, and brain were removed for a biochemical biomarker analysis, histopathological analysis, and metal quantification. As a result, we observed changes in the activity of the analyzed enzymes (SOD, GST, GPx) in the kidney and brain of the zebrafish, a reduction in GSH levels in all analyzed tissues, and a reduction in MT levels in the kidney and liver as well as in the brain. Changes in AChE enzyme activity were observed. The biochemical results corroborate the changes observed in the lesion index and histomorphology sections. We emphasize the importance of joint research on these compounds to increase the population’s safety against their possible toxic effects. Full article

Obesity is linked to neurodegeneration, which is mainly caused by inflammation and oxidative stress. We analyzed whether the long-term intake of honey and/or D-limonene, which are known for their antioxidant and anti-inflammatory actions, when ingested separately or in combination, can counteract the neurodegeneration occurring in high fat diet (HFD)-induced obesity. After 10 weeks of HFD, mice were divided into: HFD-, HFD + honey (HFD-H)-, HFD + D-limonene (HFD-L)-, HFD + honey + D-limonene (HFD-H + L)-fed groups, for another 10 weeks. Another group was fed a standard diet (STD). We analyzed the brain neurodegeneration, inflammation, oxidative stress, and gene expression of Alzheimer’s disease (AD) markers. The HFD animals showed higher neuronal apoptosis, upregulation of pro-apoptotic genes Fas-L, Bim P27 and downregulation of anti-apoptotic factors BDNF and BCL2; increased gene expression of the pro-inflammatory IL-1β, IL-6 and TNF-α and elevated oxidative stress markers COX-2, iNOS, ROS and nitrite. The honey and D-limonene intake counteracted these alterations; however, they did so in a stronger manner when in combination. Genes involved in amyloid plaque processing (APP and TAU), synaptic function (Ache) and AD-related hyperphosphorylation were higher in HFD brains, and significantly downregulated in HFD-H, HFD-L and HFD-H + L. These results suggest that honey and limonene ingestion counteract obesity-related neurodegeneration and that joint consumption is more efficacious than a single administration. Full article

After spinal cord transection (SCT) the interaction between motoneurons (MNs) and muscle is impaired, due to reorganization of the spinal network after a loss of supraspinal inputs. Rats subjected to SCT, treated with intraspinal injection of a AAV-BDNF (brain-derived neurotrophic factor) construct, partially regained the ability to walk. The central effects of this treatment have been identified, but its impact at the neuromuscular junction (NMJ) has not been characterized. Here, we compared the ability of NMJ pre- and postsynaptic machinery in the ankle extensor (Sol) and flexor (TA) muscles to respond to intraspinal AAV-BDNF after SCT. The gene expression of cholinergic molecules (VAChT, ChAT, AChE, nAChR, mAChR) was investigated in tracer-identified, microdissected MN perikarya, and in muscle fibers with the use of qPCR. In the NMJs, a distribution of VAChT, nAChR and Schwann cells was studied by immunofluorescence, and of synaptic vesicles and membrane active zones by electron microscopy. We showed partial protection of the Sol NMJs from disintegration, and upregulation of the VAChT and AChE transcripts in the Sol, but not the TA MNs after spinal enrichment with BDNF. We propose that the observed discrepancy in response to BDNF treatment is an effect of difference in the TrkB expression setting BDNF responsiveness, and of BDNF demands in Sol and TA muscles. Full article

The representative clinical features of adhesive capsulitis of the hip (ACH) are restricted range of motion (ROM) and pain. However, reports on kinetics such as strength and dynamic balance that explain physical functions are rare. This study compared subjective hip scores using Copenhagen Hip and Groin Outcome Score (HAGOS) and ROM using a manual goniometer as well as strength using isokinetic equipment, and dynamic balance through the Y-balance test, between patients with ACH and healthy individuals. Data of 193 middle-aged participants (men: 99 and women: 94) were analyzed. The ACH group scored significantly lower in all six HAGOS sub-sections. Hip joint flexion, abduction, internal and external rotation ROM were significantly lower in ACH compared to healthy group. These results were the same for men and women. In the strength of men and women, flexion, adduction, and abduction, and dynamic balance in all three directions were significantly decreased in ACH. Meanwhile, there were no significant between-group differences in the functional decrease in extension and adduction of ROM, and extension strength. In conclusion, subjective evaluation and dynamic balance of patients with ACH were decreased in the all parts. In ROM, flexion, abduction, internal rotation, and external rotation were restricted except for extension and adduction. Men and women with ACH maintained extensor strength, but had weakened strength in flexion, adduction and abduction. This information will be useful for therapists to understand the biomechanical properties of ACH and to design effective rehabilitation programs. Full article

Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as “long COVID-19”. Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic. Full article

Visual evoked potentials (VEP) are changes in potentials that arise in the central nervous system. In the interpretation of the VEP test results, it is assumed that the elongation of the latency time is caused by the demyelination of the nerve fibers, and the axon damage is responsible for the decrease in the amplitude. The observed VEP deviations are not specific for specific diseases, but indicate disturbances in visual conductivity. VEP may play a diagnostic role in the early detection of visual involvement. The aim of the study was the functioning of visual pathway assessment on the basis of visual evoked potentials (VEP) examination, in patients with primary Sjögren’s Syndrome (pSS), without focal symptoms of central nervous system disorder. The effect of disease activity, as assessed by clinical parameters and antibody levels (anti-Ro52, SSA, and SSB), on the central nervous system was also evaluated. Thirty-two consecutive patient with pSS (31 females, 1 male) were included in the study. VEP was performed at baseline, and after 6 (T6) years. Their results were compared longitudinally between the baseline and T6, depending on the duration of the disease and treatment. The immunological activity of pSS was also analyzed. The group of patients showed a significant prolongation of the P100 implicit time (105.5 ± 5.1 vs. 100.6 ± 3.9; p = 0.000) and a significant higher the P100-N145 amplitude (12.3 ± 4.1 vs. 9.4 ± 3.0; p = 0.000). Abnormalities in electrophysiological parameters of VEP at baseline correlated with presentation of anti-Ro52 antibodies and aching joints. At baseline, the P100 implicit time was shorter for the patients with pSS than for those at T6 (105.50 ± 5.1 vs. 109.37 ± 5.67; p = 0.002). pSS patients without CNS involvement presented with dysfunction of visual pathway, as revealed by VEP abnormalities. Relationships were found between VEP parameters and with present of anti-Ro52 antibodies and aching joints. VEP may be a useful method for assessment and monitoring of subclinical visual deficit in the course of pSS. Full article

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis, but is not the only player with an angiogenic function. Fibroblast growth factor-2 (FGF2), which was discovered before VEGF, is also an angiogenic growth factor. It has been shown that FGF2 plays positive pathophysiological roles in tissue remodeling, bone health, and regeneration, such as the repair of neuronal damage, skin wound healing, joint protection, and the control of hypertension. Targeting FGF2 as a therapeutic tool in disease treatment through clinically useful inhibitors has not been developed until recently. An isolated inhibitory RNA aptamer against FGF2, named RBM-007, has followed an extensive preclinical study, with two clinical trials in phase 2 and phase 1, respectively, underway to assess the therapeutic impact in age-related macular degeneration (wet AMD) and achondroplasia (ACH), respectively. Moreover, showing broad therapeutic potential, preclinical evidence supports the use of RBM-007 in the treatment of lung cancer and cancer pain. Full article