PeerJ最新文献

{"title":"Mitigative effect of sodium alginate on streptozotocin (STZ)-induced diabetic neuropathy through regulation of redox status and miR-146a in the rat sciatic nerve.","authors":"Nema A Mohamed, Naeimah M Shouran, Amina E Essawy, Ashraf M Abdel-Moneim, Sherine Abdel Salam","doi":"10.7717/peerj.19046","DOIUrl":"10.7717/peerj.19046","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is a significant complication of diabetes with limited effective therapeutic options. Sodium alginate (SA), a natural polysaccharide from brown algae, has demonstrated health benefits, however, whether it can treat streptozotocin (STZ)-induced DPN remains unclear. The present experiment aimed to test the preventive role of SA on STZ-induced DPN in rats and explored the possible mechanisms. The DPN rat model was established in rats by intraperitoneal injection of a single dose of 40 mg/kg b.w. STZ, and SA (200 mg/kg b.w./day) was orally administered for 28 days after type 2 diabetes mellitus (T2DM) induction. The obtained findings revealed that STZ significantly increased serum levels of FBG, HOMA-IR, TC, TG, VLDL-C, and LDL-C, while decreased serum insulin, incretin GLP-1, HDL-C, and lipase activity. In the sciatic nerves, STZ significantly increased proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α), caspase-3 (a pro-apoptotic protein), markers of oxidative stress (MDA and NO), and AGEs. In parallel, STZ induced a significant decline in the activities of enzymatic antioxidants, <i>viz.</i>, SOD, CAT, and GPx, and non-enzymatic GSH. These changes were accompanied by a low expression of miR-146a in the sciatic nerves of DPN rats. Except for HOMA-IR, SA treatment to STZ injected rats significantly improved these parameters and helped to rescue the neurological morphology of the sciatic nerve fibers. In conclusion, SA mitigated experimental DPN, and this might be due to its ability to suppress hyperglycemic-hyperlipidemic effects, counteract the overactivation of inflammatory molecules, increase miR-146a expression, modulate oxidative dysregulation, and reduce cell apoptosis.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19046"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyunsaturated fatty acids and their endocannabinoid-related metabolites activity at human TRPV1 and TRPA1 ion channels expressed in HEK-293 cells.","authors":"Atnaf Abate, Marina Santiago, Alfonso Garcia-Bennett, Mark Connor","doi":"10.7717/peerj.19125","DOIUrl":"10.7717/peerj.19125","url":null,"abstract":"<p><strong>Background: </strong>Polyunsaturated fatty acids (PUFAs), particularly Omega-3 (ω-3) and Omega-6 (ω-6) PUFAs, may exert neuroprotective effects via the endocannabinoid system (ECS) and are promoted as brain health supplements. However, despite their potential role in endocannabinoid biosynthesis, the impact of PUFAs on ion channels such as TRPV1 and TRPA1, which are modulated by endocannabinoids, remains incompletely understood. Furthermore, the potential <i>in vitro</i> actions of ω-6 and ω-3 PUFA combined in the ratios available in supplements remains uncertain. Therefore, the objective of this study is to evaluate the functional activity of individual PUFAs, their combination in a specific ratio, and their endocannabinoid-related derivatives on TRPV1 and TRPA1 ion channels.</p><p><strong>Methodology: </strong>We employed a fluorescent calcium-sensitive dye in HEK-293 Flp-In T-REx cells expressing human TRPV1, TRPA1, or an empty vector to measure changes in intracellular calcium concentration ([Ca]_i).</p><p><strong>Results: </strong>Capsaicin and PUFA derivatives such as docosahexaenoyl ethanolamide (DHEA), γ-linolenoyl ethanolamide (γ-LEA) and anandamide (AEA) stimulate TRPV1 activity directly, whereas eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and their 9:3:1 ratio triggered TRPV1 response only after prior exposure to phorbol ester. Cinnamaldehyde and PUFA derivatives such as eicosapentaenoyl ethanolamide (EPEA), DHEA, γ-LEA, 2-arachidonoylglycerol (2-AG), 2-arachidonoylglycerol ether (2-AG ether) and AEA triggered TRPA1 response, with EPA, DHA, γ-LA, and the 9:3:1 ratio showing significant effects at higher concentrations.</p><p><strong>Conclusions: </strong>PUFAs alone and their combined form in 9:3:1 ratio stimulate TRPA1 activity, whereas their metabolites trigger both TRPV1 and TRPA1 response. These findings suggest new avenues to explore for research into potential mechanisms underlying the neurological benefits of PUFAs and their metabolites.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19125"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spatial and temporal evolution of habitat quality and driving factors in nature reserves: a case study of 33 forest ecosystem reserves in Guizhou Province.","authors":"Xuemeng Mei, Yi Liu, Li Yue, Mingming Zhang","doi":"10.7717/peerj.19098","DOIUrl":"10.7717/peerj.19098","url":null,"abstract":"<p><strong>Background: </strong>Biodiversity plays a crucial role for humanity, serving as a foundation for human survival and development. Habitat quality serves as a critical indicator for assessing biodiversity and holds significant importance in both theoretical and practical domains. The unique natural geographical environment of Guizhou Province has fostered rich biodiversity and facilitated the establishment of numerous nature reserves, predominantly centered on forest ecosystems. Analyzing the habitat quality of nature reserves and its influencing factors is of great significance for maintaining the regional ecosystem stability, promoting sustainable development, and improving the ecological environment.</p><p><strong>Method: </strong>Therefore, taking the 33 nature reserves of forest ecosystem in Guizhou Province as the study area, we first quantified habitat quality using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model to analyze changes in the nature reserve from 2000 to 2020. Then, we explored the effects of natural and social factors on the spatiotemporal evolution of habitat quality using the optimal parameters-based geographical detector (OPGD).</p><p><strong>Results: </strong>Forests were identified as the primary land-use type in the study area. However, the nature reserves saw an increase area in cropland, and impervious land by 5,001.39 ha and 102.15 ha; a significant decrease in forests and grasslands; and a slight decrease in watersheds. Rapid urbanization, therefore, negatively affected the overall habitat quality of the reserve. Although there is a declining trend in the habitat quality of the nature reserve, the magnitude of change from 2010 to 2020 (-0.04) is smaller than that from 2000 to 2010 (-0.17), indicating that the management of the reserve has been somewhat effective. In national-level nature reserves, interactions between natural geographic factors and socio-economic factors were greater than interactions between natural geographic factors. Similarly, in local-level nature reserves, interactions between natural geographic factors and socio-economic factors outweighed interactions among social factors.</p><p><strong>Conclusion: </strong>The spatiotemporal variability of habitat quality in the study area was shaped by the combined effects of natural and social factors. The habitat quality of local-level protected areas is, furthermore, more significantly affected by human activities, which are the primary cause of their degradation.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19098"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum ferritin associated with atherogenic lipid profiles in a high-altitude living general population.","authors":"Menglong Jin, Mawusumu Mamute, Hebali Shapaermaimaiti, Hongyu Ji, Zichen Cao, Sifu Luo, Mayire Abudula, Abuduhalike Aigaixi, Zhenyan Fu","doi":"10.7717/peerj.19104","DOIUrl":"10.7717/peerj.19104","url":null,"abstract":"<p><strong>Background: </strong>Serum ferritin (SF) levels are associated with metabolic syndrome and dyslipidemia. However, the association between SF and atherogenic lipid profiles in high-altitude living populations remains unclear.</p><p><strong>Methods: </strong>In 2021, a cross-sectional study was conducted on adult Tajik individuals residing in Tashkurgan Tajik Autonomous County (average altitude 3,100 meters). Demographic information and anthropometric measurements were collected in local clinics. Fasting blood samples were analyzed using a Beckman AU-680 Automatic Biochemical analyzer at the biochemical laboratory of Fuwai Hospital. Univariate linear regression analyses were used to explore the association between SF and atherogenic lipid levels. Subgroup analysis was used based on gender and different high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA) levels. The association between higher SF quartiles and different kinds of dyslipidemia were analyzed by logistic regression.</p><p><strong>Results: </strong>There were 1,703 participants in total, among which 866 (50.9%) being men. The mean ages of male and female participants were similar (41.50 <i>vs.</i> 42.38 years; <i>P</i> = 0.224). SF levels were significantly correlated with total cholesterol (TC) (Beta = 0.225, <i>P</i> < 0.001), low-density lipoprotein cholesterol (LDL-C) (Beta = 0.197, <i>P</i> < 0.001), high-density lipoprotein cholesterol (HDL-C) (Beta = -0.218, <i>P</i> < 0.001), triglycerides (TG) (Beta = 0.332, <i>P</i> < 0.001), and small dense LDL-C (sdLDL-C) (Beta = 0.316, <i>P</i> < 0.001), with the exception of lipoprotein (a) (Lp(a)) (Beta = 0.018, <i>P</i> = 0.475). SF was significantly correlated with LDL-C and HDL-C in women, and correlated with TC, TG, and sdLDL-C levels in both men and women in different inflammatory conditions. Elevated SF levels was significantly correlated with high TC (OR: 1.413, 95% CI [1.010-1.978]), high TG (OR: 1.602, 95% CI [1.299-1.976]), and high sdLDL-C (OR: 1.631, 95% CI [1.370-1.942]) in men and high TC (OR: 1.461, 95% CI [1.061-2.014]), high LDL-C (OR: 2.104, 95% CI [1.481-2.990]), low HDL-C (OR: 1.447, 95% CI [1.195-1.752]), high TG (OR: 2.106, 95% CI [1.454-3.050]), and high sdLDL-C (OR: 2.000, 95% CI [1.589-2.516]) in women. After adjusting for potential confounders, elevated SF levels continue to be correlated with high TG in male (OR: 1.382, 95% CI [1.100-1.737]) and female (OR: 1.677, 95% CI [1.070-2.628]) participants. In both young and middle-aged subgroups, the associations between SF and TG, TC, HDL-C, LDL-C, and sdLDL-C were still significant.</p><p><strong>Conclusions: </strong>SF was closely related to atherogenic lipid profiles, especially with regard to TG in high-altitude populations. This association cannot be attributed to its role as an inflammation marker.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19104"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demographics and physical and mental health of clients at a sports center with and without exercise addiction.","authors":"Rasmon Kalayasiri, Chayamon Rattanawijarn","doi":"10.7717/peerj.19002","DOIUrl":"10.7717/peerj.19002","url":null,"abstract":"<p><strong>Background: </strong>While exercise is widely recognized for its health benefits, excessive engagement can lead to exercise addiction (EA), a behavioral condition characterized by compulsive and harmful physical activity. Limited research exists on the demographic, physical, and mental health profiles of individuals with EA. This descriptive cross-sectional study examines demographic factors and related health outcomes among clients at a university sports center with and without EA.</p><p><strong>Methods: </strong>A total of 386 participants were randomly recruited through convenience sampling at the Chulalongkorn University Sports Center in Bangkok, Thailand. EA, physical well-being, and mental well-being were assessed using the Exercise Addiction Inventory (EAI), the Knee and Osteoarthritis Outcome Score (KOOS), and the Questionnaire for Eudaimonic Well-Being (QEWB), respectively. Demographic and exercise-related variables, psychological well-being, and knee outcomes were compared between participants with and without EA using Chi-square tests. Logistic regression analysis was performed to identify predictors of EA.</p><p><strong>Results: </strong>The majority of participants were male (55.2%), with a mean age of 27.5 years (SD = 10.9). Among the 386 participants, 322 (83.4%) exhibited partial symptoms, and 35 (9.1%) exhibited full symptoms of EA. Full symptoms of EA were significantly associated with gender, exercise frequency, smoking status, hours spent walking, hours spent in other sports, cognitive focus on metabolism during exercise, and poor knee outcomes (<i>P</i> < 0.05). Logistic regression revealed that being male was the sole significant predictor of EA (OR = 2.65, <i>P</i> = 0.024).</p><p><strong>Conclusions: </strong>EA was prevalent among clients at the sports center and was associated with adverse knee outcomes. Being male was identified as a key predictor of EA. Future research should explore additional factors associated with EA and its effects on physical and mental health.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19002"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of atrial fibrosis on clot burden score and physicochemical properties of thrombus in patients with ischaemic stroke occurring in non-valvular atrial fibrillation.","authors":"Juan Zhao, Guangjun Deng, Weijing Wang, Peng Wang, Xinyu Shen, Xiaoxiao Yuan, Haifei Jiang, Zhong-Bao Ruan","doi":"10.7717/peerj.19173","DOIUrl":"10.7717/peerj.19173","url":null,"abstract":"<p><strong>Background: </strong>To investigate the effect of the degree of atrial fibrosis on the clot burden score (CBS) and physicochemical properties in patients with acute ischaemic stroke (AIS) due to non-valvular atrial fibrillation (NVAF).</p><p><strong>Methods: </strong>A total of 117 patients with AIS in NVAF attending the Department of Cardiovascular Medicine and the Cerebrovascular Diagnostic and Treatment Centre between August 2021 and May 2024 were included in the study. Baseline clinical data, biochemical indexes, and imaging data of the patients were collected, and the patients were divided into 93 cases of the CBS (score of 0-6) group and 24 cases of the CBS (score of 7-10) group according to the CBS. CBS (score of 0-6) signifies higher clot burden. The enzyme-linked immunosorbent assay was used to measure the concentration of galactaglutinin-3 (gal-3) and transforming growth factor (TGF-β1) in the serum of the patients, and the PTFV1 were collected by 12-lead electrocardiogram, and the differences in the degree of atrial fibrosis between different groups and the risk factors of CBS (score of 0-6) were analysed. To analyse the effect of atrial fibrosis on the collateral circulation of stroke, the patients were divided into 31 cases with good collateral circulation (grade 3-4) and 86 cases with poor collateral circulation (grade 0-2) according to the digital subtraction angiography (DSA) images. The cerebral thrombus was collected from 60 AIS patients who underwent mechanical thrombectomy. The content of erythrocyte, fibrin/platelets and leukocytes in the thrombus was analysed by Mathew's scarlet blue staining, and the density of thrombus was measured by computed tomography (CT).</p><p><strong>Results: </strong>A total of 117 patients were included in this study, and the proportion of hypertensive patients, proportion of chronic atrial fibrillation (CAF), B-type natriuretic peptide (BNP), neutrophil/lymphocyte ratio (NLR), D-dimer, uric acid concentration, proportion of patients with PTFV1 < -0.03 mm s, gal-3, and TGF-β1 were higher in the CBS (score of 0-6) group as compared to the CBS (score of 7-10) group (<i>P</i>-value < 0.05). Hypertension, proportion of CAF, homocysteine, NLR, D-dimer, uric acid, PTFV1 < -0.03 mm s, gal-3, and TGF-β1, were risk factors for the development of high CBS in atrial fibrillation (AF), and hypertension and CAF were the most important factors for the occurrence of AF in the independent risk factors for stroke combined with high clot burden. gal-3 and TGF-β1 were risk factors for poor collateral circulation, atrial fibrosis indexes were not associated with thrombus pathological composition and thrombus density.</p><p><strong>Conclusions: </strong>Atrial fibrosis increases clot burden in patients with AIS due to NVAF but does not significantly correlate with the physicochemical properties and density of the thrombus.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19173"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and biological characterization of pathogen causing sooty blotch of <i>Ardisia crispa</i> (Thunb.) A.DC.","authors":"Demei Yang, Jiangli Luo, Ying Zhou, Sixuan Zhou, Xiongwei Liu, Chang Liu","doi":"10.7717/peerj.19130","DOIUrl":"10.7717/peerj.19130","url":null,"abstract":"<p><p>Sooty blotch, a primary leaf disease affecting <i>Ardisia crispa</i> (Thunb.) A.DC. (<i>A. crispa</i>, AC), significantly impacts both the yield and quality of this medicinal plant. However, the specific species of pathogenic fungi responsible for this disease and their mechanisms of pathogenesis remain unclear. To elucidate the etiology of sooty blotch, it is essential to investigate effective prevention and treatment methods, and provide a theoretical basis for the effective protection of AC. Initially, the alterations in internal organelles that result in sooty blotch were examined using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Additionally, differential genes were analyzed using differential display reverse transcriptase-PCR (DDRT-PCR) in both healthy and diseased leaves of AC. Moreover, the pathogenic fungi were separated, purified and identified from leaves infected with sooty blotch of AC, and subsequently, their pathogenicity and biological characteristics were tested. Furthermore, the inhibitory effect of pathogens was measured using the water extract of traditional Chinese medicine, based on the growth rate of the mycelium. The findings indicated that the photosynthesis rate of diseased leaves was slower than that of healthy leaves, as revealed by TEM and SEM analyses. Additionally, DDRT-PCR results demonstrated that the differentially expressed genes primarily included those related to zinc finger proteins, acyl-CoA-transferases, and chloroplasts. The phylogenetic tree and pathogenicity test results showed that the pathogens causing sooty blotch of AC were <i>Annulohypoxylon stygium</i> and <i>Diaporthe angelicae</i>. Microscopic observation revealed that <i>Annulohypoxylon stygium</i> and <i>Diaporthe angelicae</i> exhibited distinct microscopic characteristics, and a pH range of 7-10 along with a subdued light environment were more conducive to the growth of pathogens. Additionally, the water extract of <i>Lonicera fulvotomentosa</i> Hsu et S. C. Cheng and <i>A. crispa</i> (Thunb.) A.DC. had a strong antifungal action on the two pathogens of sooty blotch, and the water extract of Ardisia crenate Sims had a better antifungal action on the <i>Diaporthe</i> <i>angelicae</i>. In this study, <i>Annulohypoxylon stygium</i> and <i>Diaporthe</i> <i>angelicae</i> were reported as pathogenic fungi causing sooty blotch for the first time, and affected the photosynthesis of AC leaf, and these study provides a theoretical basis for the diagnosis and prevention of <i>A. crispa</i> (Thunb.) A.DC. sooty blotch.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19130"},"PeriodicalIF":2.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of an immunoinformatics-based multi-epitope vaccine candidate targeting Kyasanur forest disease virus.","authors":"Sunitha Manjari Kasibhatla, Lekshmi Rajan, Anita Shete, Vinod Jani, Savita Yadav, Yash Joshi, Rima Sahay, Deepak Y Patil, Sreelekshmy Mohandas, Triparna Majumdar, Uddhavesh Sonavane, Rajendra Joshi, Pragya Yadav","doi":"10.7717/peerj.18982","DOIUrl":"10.7717/peerj.18982","url":null,"abstract":"<p><p>Kyasanur forest disease (KFD) is one of the neglected tick-borne viral zoonoses. KFD virus (KFDV) was initially considered endemic to the Western Ghats region of Karnataka state in India. Over the years, there have been reports of its spread to newer areas within and outside Karnataka. The absence of an effective treatment for KFD mandates the need for further research and development of novel vaccines. The present study was designed to develop a multi-epitope vaccine candidate against KFDV using immunoinformatics approaches. A total of 74 complete KFDV genome sequences were analysed for genetic recombination followed by phylogeny. Computational prediction of B- and T-cell epitopes belonging to envelope protein was performed and epitopes were prioritised based on IFN-Gamma, IL-4, IL-10 stimulation and checked for allergenicity and toxicity. The eight short-listed epitopes (three MHC-Class 1, three MHC-Class 2 and two B-cell) were then combined using various linkers to construct the vaccine candidate. Molecular docking followed by molecular simulations revealed stable interactions of the vaccine candidate with immune receptor complex namely Toll-like receptors (TLR2-TLR6). Codon optimization followed by <i>in-silico</i> cloning of the designed multi-epitope vaccine construct into the pET30b (+) expression vector was carried out. Immunoinformatics analysis of the multi-epitope vaccine candidate in the current study has potential to significantly accelerate the initial stages of vaccine development. Experimental validation of the potential multi-epitope vaccine candidate remains crucial to confirm effectiveness and safety in real-world conditions.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e18982"},"PeriodicalIF":2.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic model of low-grade glioma based on m6A-associated immune genes and functional study of FBXO4 in the tumor microenvironment.","authors":"Yiling Zhang, Na Luo, Xiaoyu Li, Chuanfei Zeng, Xin Chen, Xiaohong Peng, Yuanyuan Zhang, Guangyuan Hu","doi":"10.7717/peerj.19194","DOIUrl":"10.7717/peerj.19194","url":null,"abstract":"<p><strong>Background: </strong>m6A plays a dual role in regulating the expression of oncogenes and tumor suppressor genes, and is crucial in tumorigenesis and progression. The immune system is closely involved in tumorigenesis and development, playing a key role in tumor therapy and resistance. However, research on m6A-related immune markers in low-grade gliomas is still limited and requires further investigation.</p><p><strong>Methods: </strong>All data was obtained from the Chinese Glioma Genome Atlas database and The Cancer Genome Atlas. The construction of the prognostic model and the online application of the dynamic nomogram relied on univariate Cox analysis, LASSO regression, and multivariate Cox analysis. Two different clustering analyses were performed on all samples, resulting in high, medium, and low expression groups of m6A regulatory and immune genes, followed by an analysis of the correlations between these scores. Finally, the biological role of FBXO4 in glioma cells was determined through quantitative reverse transcription polymerase chain reaction, cell proliferation assays, and cell migration experiments.</p><p><strong>Results: </strong>The prognostic model for low-grade glioma demonstrated strong performance, with an AUC over 0.9 in the training group. In the internal validation group, AUC values ranged from 0.831 to 0.894, while in the external validation group, the AUC ranged from 0.623 to 0.813. Additionally, the online application of the dynamic nomogram allowed for relatively accurate predictions of LGG patients' survival time. Further analysis revealed that the high-expression groups of m6A regulatory genes and m6A-related immune genes exhibited higher levels of immune cells and stromal cells, lower tumor purity, and poorer survival rates. GSEA enrichment analysis suggested that these findings might be related to the activation of multiple signaling pathways. This may explain the lower survival rates observed in this group. Furthermore, the m6A score was significantly associated with moderate to high expression of immune genes and high expression of m6A regulatory genes, and it showed a positive correlation with most immune cell types. Finally, <i>in vitro</i> experiments confirmed that silencing FBXO4 significantly inhibited proliferation and migration in glioma cell lines, further supporting the biological relevance of our model.</p><p><strong>Conclusion: </strong>Based on multi-dimensional clustering analysis and experimental validation, the prognostic model developed in this study can effectively assess the prognosis of LGG patients and their relationship with the immune microenvironment. Furthermore, the correlation analysis between m6A scores and the tumor microenvironment provides a foundation for further exploration of the disease's pathophysiology. Additionally, we suggest that FBXO4 may serve as an important biomarker for the diagnosis and prognosis of LGG.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19194"},"PeriodicalIF":2.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative genomic analysis of emerging non-typeable <i>Haemophilus influenzae</i> (NTHi) causing emerging septic arthritis in Atlanta.","authors":"Brianna J Bixler, Charlotte J Royer, Robert A Petit Iii, Abraham G Moller, Samantha Sefton, Stepy Thomas, Amy Tunali, Lauren F Collins, Monica M Farley, Sarah W Satola, Timothy D Read","doi":"10.7717/peerj.19081","DOIUrl":"10.7717/peerj.19081","url":null,"abstract":"<p><strong>Background: </strong><i>Haemophilus influenzae</i> is a Gram-negative bacterium that can exist as a commensal organism or cause a range of diseases, from ear infections to invasive conditions like meningitis. While encapsulated <i>H. influenzae</i> strains have historically been linked to severe diseases, non-typeable <i>Haemophilus influenzae</i> (NTHi) strains, lacking an intact capsule locus, have emerged as the leading cause of invasive <i>H. influenzae</i> infections, particularly following the widespread use of the <i>H. influenzae</i> serotype b (Hib) vaccine.</p><p><strong>Methods: </strong>In response to a significant increase in invasive NTHi infections among persons living with HIV in metropolitan Atlanta during 2017-2018, we conducted a comparative genomic analysis of two predominant NTHi clones, C1 and C2, identified during this period. These clones correspond to multilocus sequence types ST164 and ST1714, respectively. We analyzed the genomic characteristics of C1 and C2 using whole genome sequencing data and compared them to a broader pangenome of <i>H. influenzae</i> strains to identify potential virulence factors and genetic adaptations.</p><p><strong>Results: </strong>Both C1 and C2 isolates were highly related within their clusters, with C1 showing a maximum of 132 SNPs and C2 showing 149 SNPs within their respective core genomes. Genomic analysis revealed significant deletions in known virulence genes, surprisingly suggesting possible attenuation of virulence. No unique accessory genes were identified that distinguished C1 and C2 from other <i>H. influenzae</i> strains, although both clusters exhibited a consistent loss of the <i>pxpB</i> gene (encoding 5-oxoprolinase subunit), replaced by a mobile cassette containing genes potentially involved in sugar metabolism. All C1 and C2 isolates showed potential enrichment in accessory genes associated with systemic infections.</p><p><strong>Conclusions: </strong>Our study suggests that while C1 and C2 clones possess some genetic markers potentially linked to systemic infections, there are no definitive unique genetic factors that distinguish these clones as more virulent than other <i>H. influenzae</i> strains. The expansion of these clones in a vulnerable population may reflect both chance introduction and potential adaptations to the host environment. Further research is needed to understand the implications of these genetic findings on the clinical management and prevention of invasive NTHi infections.</p>","PeriodicalId":19799,"journal":{"name":"PeerJ","volume":"13 ","pages":"e19081"},"PeriodicalIF":2.3,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}