Life sciences最新文献

{"title":"The crosstalks between vascular endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts in vascular remodeling.","authors":"Ming Xie, Xiandeng Li, Lun Chen, Yufeng Zhang, Long Chen, Haibing Hua, Jia Qi","doi":"10.1016/j.lfs.2024.123319","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123319","url":null,"abstract":"<p><p>Pathological vascular remodeling (VR) is characterized by structural and functional alterations in the vascular wall resulting from injury, which significantly contribute to the development of cardiovascular diseases (CVDs). The vascular wall consists primarily of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and adventitial fibroblasts (AFs), whose interactions are crucial for both the formation of the vascular system and the maintenance of mature blood vessels. Disruptions in the communication between these cell types have been implicated in the progression of VR. This review examines the complex interactions between ECs, VSMCs, and AFs in the context of CVD development, emphasizing a relatively underexplored yet potentially critical mechanism. This interaction framework likely extends to the broader cellular dialogue in the pathogenesis of CVDs, suggesting novel therapeutic strategies for intervention.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123319"},"PeriodicalIF":5.2,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased lamina propria B cells play roles in fructose-induced hypertension of Dahl salt-sensitive rats.","authors":"Sungmin Jang, Cheong-Wun Kim, Zainab Yetunde Olarinoye, Sadia Akter, Inkyeom Kim","doi":"10.1016/j.lfs.2024.123314","DOIUrl":"10.1016/j.lfs.2024.123314","url":null,"abstract":"<p><strong>Aims: </strong>Although the immune system participates in the development of hypertension, the proportional contributions of distinct immune cells remain poorly understood. With the development of transcriptomics, we can profile the transcriptomes of individual immune cells and assess the relative contribution of each immune cell to the development of hypertension. So, we tested the hypothesis that increased lamina propria B cells play roles in fructose-induced hypertension of Dahl salt-sensitive (SS) rats.</p><p><strong>Materials and methods: </strong>Eight-week-old Dahl SS and Dahl salt-resistant (SR) male rats were divided into four groups; each group received either tap water (TW) or a 20 % fructose solution (HFS) for 4 weeks. Systolic blood pressure was measured using the tail-cuff method. Single-cell RNA sequencing (scRNA-seq) analysis was performed on lamina propria (LP) cells and peripheral blood mononuclear cells (PBMCs) obtained from the SS and SR rats subjected to either TW or HFS.</p><p><strong>Key findings: </strong>Results revealed that high-fructose intake induced hypertension in the SS rats but not in the SR rats. It also increased B cells in LPs but not in PBMCs of the SS rats; their subsets showed increased follicular and naïve B cells. Increased lamina propria B cells play roles in fructose-induced hypertension of SS rats.</p><p><strong>Significance: </strong>This finding suggest that targeting B cells could be a potential strategy to mitigate high blood pressure in fructose-induced hypertension.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123314"},"PeriodicalIF":5.2,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice.","authors":"Flavia Maria Silva-Veiga, Thatiany Souza Marinho, Vanessa de Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda","doi":"10.1016/j.lfs.2024.123310","DOIUrl":"10.1016/j.lfs.2024.123310","url":null,"abstract":"<p><p>The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT. The ileum was structurally and molecularly studied, and cecal feces had microbial DNA determined. Tzp improved the intestinal barrier structure and protection. Cldn12 (Claudin 12) increased, and Muc2 (Mucin 2) decreased. JamA (junctional adhesion molecules) and Ocln (Occludin) increased. Tzp mitigated macrophage activation and inflammation, altered composition, and the contribution to microbiota: Firmicutes decreased, and Bacteroidetes increased, changing the Firmicutes / Bacteroidetes ratio. Proteobacteria, Actinobacteria, Bifidobacterium, and Clostridium increased. In addition, Bacteroides, Prevotella, and Akkermansia increased. PCA indicated a significant action of Cd14, Muc2, and Tlr4 on CO and Il17 on OdO; Il10, Cd206, Cd12, Ocln, and JamA in Od. Bacteroides, Bifidobacterium, Clostridium, Actinobacteria, and Bacteroides were enhanced in CT and COT, Provotella, Proteobacteria, and Firmicutes in CO, Od, OdT, OdO, and Akkermansia in OdOT. In conclusion, the intestinal barrier function in our model is compromised by alterations in phylogenetic diversity and intestinal microbiota, which characterize dysbiosis and potentially enable the influx of toxins into other tissues. Treatment with Tzp demonstrated the ability to reverse intestinal dysbiosis, help repair intestinal barrier integrity, and mitigate possible endotoxemia through anti-inflammatory signaling pathways.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123310"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smooth muscle cell-specific CD47 deletion suppresses atherosclerosis.","authors":"Naveed Pervaiz, Rashid Mehmood, Ravi Varma Aithabathula, Ishita Kathuria, WonMo Ahn, Britney-Thuy Le, Ki-Suk Kim, Udai P Singh, Gabor Csanyi, Bhupesh Singla","doi":"10.1016/j.lfs.2024.123315","DOIUrl":"10.1016/j.lfs.2024.123315","url":null,"abstract":"<p><strong>Background: </strong>Recent smooth muscle cell (SMC)-lineage tracing and single-cell RNA sequencing (scRNA-seq) experiments revealed a significant role of SMC-derived cells in atherosclerosis development. Further, thrombospondin-1 (TSP1), a matricellular protein, and activation of its receptor cluster of differentiation (CD) 47 have been linked with atherosclerosis. However, the role of vascular SMC TSP1-CD47 signaling in regulating VSMC phenotype and atherogenesis remains unknown.</p><p><strong>Methods: </strong>We investigated the role of SMC CD47 activation by TSP1 in regulating VSMC phenotype and atherosclerosis development using various in vitro cell-based assays, molecular biological techniques, immunohistological approaches, reanalysis of publicly available scRNA-seq data, and cell-specific knockout mice.</p><p><strong>Results: </strong>We observed elevated TSP1 expression in human atherosclerotic vascular tissues and VSMCs. TSP1-treated VSMCs exhibited decreased expression of contractile SMC markers (ACTA2, CNN1, and TAGLN) and increased proliferation. Additional experiments and reanalysis of the scRNA-seq dataset showed CD47 as the major TSP1 receptor in VSMCs, with its expression increased in SMC-derived modulated cells of murine atherosclerotic arteries. Knockdown of CD47 gene in human VSMCs upregulated expression of contractile SMC markers and abrogated TSP1's effects on these genes. SMC-specific Cd47 deletion in mice suppressed atherosclerotic lesion formation, reduced macrophage accumulation, and decreased necrotic area. However, no significant differences were observed in weight gain, liver and adipose tissue mass, plasma total cholesterol, and fasting blood glucose between control and SMC-restricted Cd47-deficient mice. Further experiments demonstrated increased efferocytosis of apoptotic CD47-silenced VSMCs by macrophages.</p><p><strong>Conclusions: </strong>These findings suggest that CD47 plays a crucial role in regulating VSMC phenotype, and SMC-specific-Cd47 deletion suppresses atherosclerosis.</p><p><strong>New and noteworthy: </strong>VSMC phenotypic switching contributes to atherosclerosis development. The present study reports the novel observations that Cd47 levels are upregulated in phenotypically modulated SMCs within atherosclerotic arteries and targeted deletion of Cd47 specifically in SMCs attenuates atherosclerosis. Mechanistic in vitro investigations further showed that TSP1-CD47 signaling regulates VSMC phenotype. Therefore, targeting SMC CD47 represents a promising therapeutic target to suppress atherogenesis.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123315"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMP: A dual modulator of apoptosis and autophagy via SHP-1 regulation in hepatocellular carcinoma.","authors":"Young Yun Jung, Yejin Hong, Dongwoo Nam, Amudha Deivasigamani, Acharan S Narula, Arunachalam Chinnathambi, Ojas A Namjoshi, Bruce E Blough, Sulaiman Ali Alharbi, Kam Man Hui, Gautam Sethi, Kwang Seok Ahn","doi":"10.1016/j.lfs.2024.123316","DOIUrl":"10.1016/j.lfs.2024.123316","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) poses a significant health burden due to its high incidence, and current treatment effectiveness is hindered by drug resistance. Thus, investigation of novel therapeutic approaches derived from natural sources is crucial for improving patient outcomes.</p><p><strong>Aims: </strong>This study aimed to explore the potential of Tetramethylpyrazine (TMP), bioactive alkaloid (ligustrazine) isolated from Chuanxiong (Ligusticum Wallichii), in targeting HCC by inducing apoptosis and enhancing autophagy. The study focused on elucidating the molecular mechanisms underlying anti-cancer effects of TMP.</p><p><strong>Main methods: </strong>To determine the influence of TMP on apoptosis and autophagy, Western blot analysis, annexin V assay, cell cycle analysis, acridine orange staining, and immunocytochemistry were performed. Next, the activation of the STAT3 signaling pathway and the anti-cancer effects of TMP in vivo were examined in an orthotopic HCCLM3-Lu mouse model.</p><p><strong>Key findings: </strong>TMP treatment induced apoptosis in HCCLM3 and Hep3B cells by activating key apoptotic factors while inhibiting proteins associated with cell survival and angiogenesis. Additionally, TMP enhanced autophagy by promoting the formation of autophagosomes and stimulating autophagy-related proteins. Furthermore, TMP suppressed the activation of the STAT3 signaling pathway by upregulating SHP-1, thereby inhibiting tumorigenesis and activating cell death pathways. Additionally, our in vivo research demonstrated that TMP significantly inhibited tumor growth and triggered the activation of both apoptosis and autophagy in tumor tissues.</p><p><strong>Significance: </strong>Our findings of this study demonstrate that TMP exerts a dual-action mechanism by modulating both apoptosis and autophagy, thus offering a promising strategy to overcome drug resistance in HCC.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123316"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the anti-tumor activity and reprogramming M2 macrophages by delivering siRNAs against SIRPα and STAT6 via M1 exosomes and combining with anti-PD-L1.","authors":"Mahsa Taghavi-Farahabadi, Mohammad Mahmoudi, Nazanin Mojtabavi, Farshid Noorbakhsh, Hossein Ghanbarian, Ameneh Koochaki, Seyed Mahmoud Hashemi, Nima Rezaei","doi":"10.1016/j.lfs.2024.123311","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123311","url":null,"abstract":"<p><strong>Background: </strong>The invasive property of breast cancer and the complex composition of the tumor microenvironment (TME) antibodies like anti-PD-L1, can inhibit tumor growth by promoting macrophage phagocytosis. In this research, we used anti-PD-L1 antibody and siRNAs targeting SIRPα (siSIRPα) and STAT6 (siSTAT6). The siRNAs were transported to macrophages using M1-derived exosomes.</p><p><strong>Methods: </strong>For this purpose, exosomes were isolated from the supernatant of lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Next, siSIRPα and siSTAT6 were electroporated into the M1-exosomes. M1-exosomes without siRNA or loaded with different siRNAs were used to treat M2 macrophages. Then, the polarization of macrophages was evaluated. By co-culturing of treated macrophages with 4T1 cells, anti-tumor functions of macrophages were assessed.</p><p><strong>Results: </strong>It was demonstrated that siRNA-loaded M1-exosomes induced macrophage polarization into an M1 phenotype and promoted the anti-tumor effects of macrophages as shown by a reduction in migration, invasion and proliferation of 4T1 cells, as well as an enhancement of phagocytosis of 4T1 cells by macrophages.</p><p><strong>Conclusion: </strong>This study demonstrated the potential of a multifaceted therapeutic approach targeting TAMs to enhance anti-tumor immune responses in breast cancer.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123311"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging insights on the role of Elovl6 in human diseases: Therapeutic challenges and opportunities.","authors":"Jiao Guo, Shulan Xue, Xiaohui Wang, Li Wang, Shi-Yuan Wen","doi":"10.1016/j.lfs.2024.123308","DOIUrl":"10.1016/j.lfs.2024.123308","url":null,"abstract":"<p><p>ELOVL6, elongation-of-very-long-chain-fatty acids 6, a crucial enzyme in lipid metabolism, primarily responsible for the elongation of carbon chains of C12-C16 saturated fatty acids. It plays a significant role in various human diseases, particularly those associated with metabolic disorders related to fatty acid synthesis, such as insulin resistance, non-alcoholic fatty liver disease, cancer, and cardiovascular diseases. Emerging research also links ELOVL6 to kidney diseases, neurological conditions such as epilepsy, and pulmonary fibrosis. The enzyme's expression is regulated by various factors including diet, oxidative stress, and circadian rhythms. For instance, a high-carbohydrate diet can promote an increase in ELOVL6 expression. This abnormality leads to an accumulation of long-chain fatty acids and lipid deposition, ultimately resulting in pathological consequences across multiple systems in the body. As a biological target, ELOVL6 holds promise for diagnostic and therapeutic applications, with future research expected to uncover its mechanisms and therapeutic potential, paving the way for novel interventions in multiple disease areas. Here, the expression regulation and function of ELOVL6 in various human diseases are reviewed. This review underscores ELOVL6 as a significant therapeutic target for human diseases, with its potential for diagnostic and therapeutic applications anticipated to drive future research and enable innovative interventions in various pathological conditions.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123308"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The underlying mechanism and therapeutic potential of IFNs in viral-based cancers.","authors":"Yu-Xin Zhu, Zi-Yi Li, Zi-Lu Yu, Yu-Tong Lu, Jia-Xiang Liu, Jian-Rui Chen, Zhen-Zhen Xie","doi":"10.1016/j.lfs.2024.123301","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123301","url":null,"abstract":"<p><p>Interferons (IFNs) are a diverse family of cytokines secreted by various cells, including immune cells, fibroblasts, and certain viral-parasitic cells. They are classified into three types and encompass 21 subtypes based on their sources and properties. The regulatory functions of IFNs closely involve cell surface receptors and several signal transduction pathways. Initially investigated for their antiviral properties, IFNs have shown promise in combating cancer-associated viruses, making them a potent therapeutic approach. Most IFNs have been identified for their role in inhibiting cancer; however, they have also demonstrated cancer-promoting effects under specific conditions. These mechanisms primarily rely on immune regulation and cytotoxic effects, significantly impacting cancer progression. Despite widespread use of IFN-based therapies in viral-related cancers, ongoing research aims to develop more effective treatments. This review synthesizes the signal transduction pathways and regulatory capabilities of IFNs, highlighting their connections with viruses, cancers, and emerging clinical treatments.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123301"},"PeriodicalIF":5.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for functional interaction between the CB1 and the mGlu7 receptors mediated signaling in modulation of anxiety behavior and cognition.","authors":"Barbara Chruścicka-Smaga, Magdalena Sowa-Kućma, Patrycja Pańczyszyn-Trzewik, Bartosz Bobula, Agata Korlatowicz, Katarzyna Latocha, Paulina Pabian, Ewelina Czechowska, Tomasz Lenda, Agata Faron-Górecka, Katarzyna Stachowicz","doi":"10.1016/j.lfs.2024.123313","DOIUrl":"10.1016/j.lfs.2024.123313","url":null,"abstract":"<p><p>Anxiety is a severe social problem. It is a disease entity that occurs alone or accompanies other diseases such as depression, phobia, or post-traumatic stress disorder. Our earlier studies demonstrated that blockage of arachidonic acid (AA) pathway via inhibition of cyclooxygenase-2 (COX-2) enzyme can modulate mGluRs-induced anxiety-like behavior. Here, we hypothesized that modulation of 2-arachidoglycerol (2-AG), a component of the AA pathway, concomitantly with modulation of mGluR7 signaling, should be adequate to trigger a similar response from the test organism. Since 2-AG is an endogenous agonist for CB1 receptors, we used a CB1/GPR55/μ-opioid receptor antagonist (AM251) alone and in combination with mGluR7 allosteric agonist (AMN082). Stress-induced hyperthermia (SIH) test was performed as a behavioral readout. AM251 has a dual mode on AMN082-mediated effects in SIH in CD-1 mice. Furthermore, the CB1 receptor ligand influenced adaptation to stress in repeated SIH procedures and learning possibilities of mice in the Barnes maze. We also found changes in mGluR7 protein expression levels in the prefrontal cortex (PFC) after mice were exposed to AM251, which showed the potential to attenuate the AMN082-induced decline in mGluR7 levels. The changes induced by AM251 on AMN082-mediated behavioral and biochemical effects were confirmed in electrophysiological experiments in which AM251 abolished AMN082-mediated LTP escalation in PFC. The mGluR7 overexpressed cell line was used to exclude the direct involvement of mGluR7 in AM251 activity. All the above results and the co-localization of CB1 and mGlu7 receptors detected in specific brain regions strongly suggest the specific interaction between CB1 and mGlu7 receptors and their signaling.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123313"},"PeriodicalIF":5.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of lipid nanoparticles-based vaccine to protect against vulvovaginal candidiasis (VVC): Implications for women's reproductive health.","authors":"Masood Alam Khan, Ayman M Mousa, Arwa Essa Alradhi, Khaled Allemailem","doi":"10.1016/j.lfs.2024.123312","DOIUrl":"10.1016/j.lfs.2024.123312","url":null,"abstract":"<p><strong>Aims: </strong>Vulvovaginal candidiasis (VVC) is a common women's health issue, with rising antifungal resistance. This study was aimed to prepare and evaluate the efficacy of a lipid nanoparticle-based vaccine in a murine model of VVC.</p><p><strong>Materials and methods: </strong>Dried and reconstituted vesicles containing C. albicans antigens (DRNPs-Ca-Ags) vaccine, formulated with phosphatidylcholine and cholesterol-based lipid nanoparticles via film hydration and freeze-drying. The safety evaluation of DRNPs-CaAgs was conducted by determining hepatic (AST, ALT) or renal (BUN, creatinine) biomarkers. Female mice were immunized with DRNPs-CaAgs or Alum-CaAgs, and immune responses were evaluated via antibody titers, IgG isotypes, and splenocyte proliferation. Protective efficacy of vaccine formulations was assessed through fungal burden, biofilm formation, cytokine levels, and histopathological analysis of vaginal tissues.</p><p><strong>Key findings: </strong>Mice vaccinated with DRNPs-CaAgs showed significantly enhanced immune responses, with higher antibody titers and IgG2a levels as compared to the Alum-CaAgs group. Vaginal fungal burden was dramatically reduced (665 ± 78 CFUs in DRNPs-CaAgs immunized group vs. 12,944 ± 3540 CFUs in Alum-CaAgs group, p < 0.01). Biofilm formation decreased by 45 % (p < 0.05), and inflammatory cytokines were significantly lowered. Histopathological analysis revealed minimal tissue damage in DRNPs-CaAgs vaccinated mice.</p><p><strong>Significance: </strong>The findings suggest DRNPs-CaAgs as a promising vaccine for VVC, eliciting strong immunity, reducing fungal load, and minimizing inflammation. While the reliance on a murine model is a limitation, future clinical trials are essential to evaluate its efficacy and safety in humans, offering a potential strategy to combat drug-resistant infections and improve women's reproductive health.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123312"},"PeriodicalIF":5.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}