ABSTRACT
Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.
Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccine Efficacy , Humans , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Double-Blind Method , Female , Male , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Adult , Middle Aged , Antibodies, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , Aged , Young Adult , Immunogenicity, Vaccine , Adolescent , Vaccination/methodsABSTRACT
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the COVID-19 pandemic, has profoundly impacted global healthcare systems and the trajectory of economic advancement. As nations grapple with the far-reaching consequences of this unprecedented health crisis, the administration of COVID-19 vaccines has proven to be a pivotal strategy in managing this crisis. Protein-based vaccines have garnered significant attention owing to their commendable safety profile and precise immune targeting advantages. Nonetheless, the unpredictable mutations and widespread transmission of SARS-CoV-2 have posed challenges for vaccine developers and governments worldwide. Monovalent and multivalent vaccines represent two strategies in COVID-19 vaccine development, with ongoing controversy surrounding their efficacy. This review concentrates on the development of protein-based COVID-19 vaccines, specifically addressing the transition from monovalent to multivalent formulations, and synthesizes data on vaccine manufacturers, antigen composition, pivotal clinical study findings, and other features that shape their distinct profiles and overall effectiveness. Our hypothesis is that multivalent vaccine strategies for COVID-19 could offer enhanced capability with broad-spectrum protection.
ABSTRACT
Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent kinds of cancers. Therefore, there is a pressing need to create a new risk scoring model to personalize the prognosis of OSCC patients and screen for patient-specific therapeutic agents and molecular targets. Methods: Firstly, A series of bioinformatics was performed to construct a novel ferroptosis-related prognostic model; Further, drug sensitivity analysis was used to screen for specific therapeutic agents for OSCC; Single-cell analysis was employed to investigate the enrichment of FRDEGs (ferroptosis-related differentially expressed genes) in the OSCC microenvironment; Finally, various experiments were conducted to screen and validate molecular therapeutic targets for OSCC. Results: In this study, we constructed a novel 10-FRDEGs risk scoring model. Base on the risk scoring model, we founded three potential chemotherapeutic agents for OSCC: 5Z)-7-Oxozeaenol, AT-7519, KIN001-266; In addition, FRDEGs were enriched in the epithelial cells of OSCC. Finally, we found that CA9 and CAV1 could regulate OSCC proliferation, migration and ferroptosis in vitro. Conclusion: A novel 10-FRDEGs risk scoring model can predict the prognosis of patients with OSCC.Further,5Z)-7-Oxozeaenol, AT-7519, KIN001-266 are potential chemotherapeutic agents for OSCC.Moreover, we identified CA9ãCAV1 as potential molecular target for the treatment of OSCC.Our findings provide new directions for prognostic assessment and precise treatment of oral cell squamous carcinoma.
ABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Dopamine (DA) neurons in the substantia nigra pars compacta, which have axonal projections to the dorsal striatum (dSTR), degenerate in PD. In contrast, DA neurons in the ventral tegmental area, with axonal projections to the ventral striatum, including the nucleus accumbens (NAcc) shell, are largely spared. This study aims to uncover the relative contributions of glycolysis and oxidative phosphorylation (OxPhos) to DA release in the striatum. We measured evoked DA release in mouse striatal brain slices using fast-scan cyclic voltammetry applied every two minutes. Blocking OxPhos resulted in a greater reduction in evoked DA release in the dSTR when compared to the NAcc shell, while blocking glycolysis caused a more significant decrease in evoked DA release in the NAcc shell than in the dSTR. Furthermore, when glycolysis was bypassed in favor of direct OxPhos, evoked DA release in the NAcc shell decreased by approximately 50% over 40 min, whereas evoked DA release in the dSTR was largely unaffected. These results demonstrate that the dSTR relies primarily on OxPhos for energy production to maintain evoked DA release, whereas the NAcc shell depends more on glycolysis. Consistently, two-photon imaging revealed higher oxidation levels of DA terminals in the dSTR than in the NAcc shell. Together, these findings partly explain the selective vulnerability of DA terminals in the dSTR to degeneration in PD.
Subject(s)
Corpus Striatum , Dopamine , Glycolysis , Oxidative Phosphorylation , Animals , Dopamine/metabolism , Mice , Corpus Striatum/metabolism , Male , Mice, Inbred C57BL , Dopaminergic Neurons/metabolism , Nucleus Accumbens/metabolismABSTRACT
BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.
Subject(s)
Apoptosis , Cell Movement , Cell Proliferation , Molecular Docking Simulation , Mouth Neoplasms , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Zebrafish , Animals , Mouth Neoplasms/drug therapy , Humans , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Phosphatidylinositol 3-Kinases/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Movement/drug effects , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Protein Interaction Maps , Carcinoma, Squamous Cell/drug therapy , Xenograft Model Antitumor Assays , Chromones/pharmacology , Morpholines/pharmacologyABSTRACT
Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes by impairing lipid metabolism. Single-cell transcriptomic profiling reveals increased antigen presentation and interferon pathways upon apoE3 expression. In contrast, apoE4 expression downregulates complement and lysosomal pathways, and promotes stress-related responses. Moreover, in the presence of mouse endogenous apoE, microglial apoE4 exacerbates amyloid pathology. Finally, we observed a reduction in Lgals3-positive responsive microglia surrounding amyloid plaque and an increased accumulation of lipid droplets in APOE4 human brains and induced pluripotent stem cell-derived microglia. Our findings establish critical isoform-dependent effects of microglia/CAM-expressed apoE in brain function and the development of amyloid pathology, providing new insight into how apoE4 vastly increases AD risk.
Subject(s)
Alzheimer Disease , Mice , Animals , Humans , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoprotein E4/genetics , Apolipoprotein E4/metabolism , Microglia/metabolism , Apolipoprotein E3/genetics , Apolipoprotein E3/metabolism , Plaque, Amyloid/metabolism , Plaque, Amyloid/pathology , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Brain , Homeostasis , Mice, TransgenicABSTRACT
Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.
Subject(s)
Nitrates , Nitrites , Humans , Aged , Nitrates/pharmacology , Nitrates/metabolism , Nitrites/metabolism , Nitric Oxide/metabolism , Nitrogen Dioxide/metabolism , Bacteria/metabolism , Nitrate Reductases/metabolism , Arginine/metabolismABSTRACT
External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a crucial regulatory role in this process. This review summarises our current understanding of microorganism-immune system interactions, with a focus on how these interactions impact the renewal and repair ability of tissues, including skin, bone, gut, liver, and nerves. This review concludes with a discussion of the mechanisms by which microbes act on various types of immune cells to affect tissue regeneration, offers potential strategies for using microbial therapies to enhance the regenerative repair function of tissues, and suggest novel therapeutic approaches for regenerative medicine. STATEMENT OF SIGNIFICANCE: Microbiological communities have crucial impacts on human health and illness by participating in energy collection and storage and performing various metabolic processes. External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a critical regulatory role in this process. This study reviews the important correlation between microorganisms and the immune system and investigates the mechanism of various microorganism that participate in the regeneration and repair of tissues and organs by modulating immune system.
Subject(s)
Immunity , Wound Healing , Humans , Regenerative Medicine , Immune System , SkinABSTRACT
Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].
ABSTRACT
The safety and immunogenicity of a protein-based tetravalent vaccine SCTV01E that contains spike protein ectodomain (S-ECD) of Alpha, Beta, Delta and Omicron BA.1 are assessed and compared with bivalent protein vaccine SCTV01C (Alpha and Beta variants) and monovalent mRNA vaccine (NCT05323461). The primary endpoints are the geometric mean titers (GMT) of live virus neutralizing antibodies (nAb) to Delta (B.1.617.2) and Omicron BA.1 at day 28 post-injection. The secondary endpoints include the safety, day 180 GMTs against Delta and Omicron BA.1, day 28 GMTs to BA.5, and seroresponse rates of neutralizing antibodies and T cell responses at day 28 post-injection. 450 participants, comprising of 449 males and 1 female, with a median age (range) of 27 (18-62) years, are assigned to receive one booster dose of BNT162b2, 20 µg SCTV01C or 30 µg SCTV01E and completed 4-week follow-up. All SCTV01E related adverse events (AEs) are mild or moderate and no Grade ≥3 AE, serious AE or new safety concerns are identified. Day 28 GMT of live virus neutralizing antibodies and seroresponse against Omicron BA.1 and BA.5 with SCTV01E are significantly higher than those with SCTV01C and BNT162b2. These data indicate an overall neutralization superiority with tetravalent booster immunization in men.
Subject(s)
BNT162 Vaccine , COVID-19 , Male , Humans , Female , Infant , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Blocking , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Hydatid bone disease is a zoonotic parasitic infection that is caused primarily by the tapeworm Echinococcus granulosus, and it continues to be a major public health concern in pastoral regions. The reconstruction of limb function after limb salvage surgery remains a challenge for clinicians. The purpose of this study was to determine the clinical efficacy of palliative treatment of the management of advanced pelvic hydatid bone disease. From March 2005 to December 2018, medical records and images of patients with advanced pelvic hydatid bone disease treated with surgery combined with antiparasitic chemotherapy were evaluated retrospectively. The Enneking classification was applied to determine the location of the lesion, and the Musculoskeletal Tumor Society score system was used for outcome evaluation. Fifteen patients who met the criteria were included in this study, with a mean follow-up of 4.40 ± 1.76 years. All patients received treatment with surgery combined with antiparasitic chemotherapy. The mean number of surgical interventions per patient for pelvic cystic echinococcosis was 5.3 (range, 2-9 interventions per patient). Recurrence of pelvic hydatid bone disease occurred in 5 patients and was managed successfully through repeated debridement procedures. Palliative treatment with limb salvage surgery was an effective and practical approach to the management of advanced pelvic hydatid bone disease. Standard antiparasitic chemotherapy, which included albendazole at a dose of 10 mg/kg/day administered in two daily doses for 3 to 6 months, was also considered an essential part of the overall treatment strategy.
Subject(s)
Bone Diseases , Echinococcosis , Animals , Humans , Retrospective Studies , Palliative Care , Echinococcosis/drug therapy , Echinococcosis/surgery , Albendazole/therapeutic use , Antiparasitic Agents/therapeutic use , Zoonoses/drug therapy , Bone Diseases/drug therapy , Bone Diseases/surgeryABSTRACT
Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic ß cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated ß-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low response rates and difficulty in maintaining therapeutic effects. Advanced drug delivery strategies can effectively harness immunotherapies and improve their potency while reducing their adverse effects. In this review, we briefly introduce the mechanisms of T1DM immunotherapy and focus on the current research status of the integration of the delivery techniques in T1DM immunotherapy. Furthermore, we critically analyse the challenges and future directions of T1DM immunotherapy.
Subject(s)
Diabetes Mellitus, Type 1 , Humans , Diabetes Mellitus, Type 1/drug therapy , Immunotherapy/methods , Insulin/therapeutic use , T-LymphocytesABSTRACT
OBJECTIVE: To study the effect of FAM72 on the prognosis of patients with oral squamous cell carcinoma (OSCC) and to explore the relationship between FAM72 and OSCC. DESIGN: We used a vast array of databases and analytical vehicles to assess the relation between FAM72 and OSCC, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. We made a preliminary verification of OSCC lines and tissues by real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: FAM72 was higher in OSCC than in normal tissues. Analysis of univariate COX data indicated that elevated expression of FAM72A, FAM72B, and FAM72C in OSCC was related to poor overall survival. Moreover, FAM72B and FAM72C were independent of overall survival in multiple COX regression. FAM72A-D and its coexpressed genes in Metascape were analyzed by Gene Ontology (GO), they were enriched in cellular cycle, mitotic and DNA metabolism. Gene set enrichment analysis (GSEA) demonstrated an enrichment in pathways related to cell metabolism. Additionally, high FAM72 expression related to a worse prognosis in OSCC patients. FAM72A-D linked to the infiltration of tumor immune cell in OSCC patients. We found that methylation levels are likely linked to prognosis in OSCC patients. We used RT-qPCR to ascertain the differential FAM72B and FAM72C expression levels in cancer and paracancerous tissues of OSCC, human normal oral keratinocytes (HOK), and human tongue squamous cell carcinoma (Cal-33). CONCLUSION: Our findings indicate that FAM72B and FAM72C are potential molecular markers of poor prognosis in OSCC and may act as novel targets for OSCC treatment strategies.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Tongue Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , Mouth Neoplasms/pathology , Tongue Neoplasms/genetics , Prognosis , Biomarkers, Tumor/genetics , Head and Neck Neoplasms/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Cell-cell communication plays a fundamental role in multicellular organisms. Cell-based cancer immunotherapies rely on the ability of innate or engineered receptors on immune cells to engage specific antigens on cancer cells to induce tumor kill. To improve the development and translation of these therapies, imaging tools capable of noninvasively and spatiotemporally visualizing immune-cancer cell interactions would be highly valuable. Using the synthetic Notch (SynNotch) system, we engineered T cells that upon interaction with a chosen antigen (CD19) on neighboring cancer cells induce the expression of optical reporter genes and the human-derived, magnetic resonance imaging (MRI) reporter gene organic anion transporting polypeptide 1B3 (OATP1B3). Administration of engineered T cells induced the antigen-dependent expression of all our reporter genes in mice bearing CD19-positive tumors but not CD19-negative tumors. Notably, due to the high spatial resolution and tomographic nature of MRI, contrast-enhanced foci within CD19-positive tumors representing OATP1B3-expressing T cells were clearly visible and their distribution was readily mapped. We then extended this technology onto human natural killer-92 (NK-92) cells, observing similar CD19-dependent reporter activity in tumor-bearing mice. Furthermore, we show that when delivered intravenously, engineered NK-92 cells can be detected via bioluminescence imaging in a systemic cancer model. With continued work, this highly modular imaging strategy could aid in the monitoring of cell therapies in patients and, beyond this, augment our understanding of how different cell populations interact within the body during normal physiology or disease.
Subject(s)
Neoplasms , Organic Anion Transporters , Humans , Mice , Animals , Genes, Reporter , Neoplasms/genetics , Killer Cells, Natural , Magnetic Resonance Imaging/methods , Organic Anion Transporters/genetics , Cell Line, TumorABSTRACT
The current study investigated the effects of Chinese young adult users' perceived information overload (i.e., the daily perception of exposure to excessive information) on their intention to stop using short-form video applications. Specifically, this study accomplished this by measuring the direct and indirect effects of social media fatigue, maladaptive coping, and life dissatisfaction in relation to users' intention to discontinue their use of short-form video applications. The data were collected using a web-based survey and validated questionnaire, with a sample of 340 young adult (18-26 years old) respondents. The results indicated that perceived information overload had a direct effect on the intention to discontinue the use of short-form video applications. Moreover, short-form video fatigue, maladaptive coping, and life dissatisfaction all played mediating roles in the relationship between perceived information overload and the intention to discontinue the use of short-form video applications among young adults in China.
ABSTRACT
Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.
Subject(s)
Microbiota , Saliva , Humans , Saliva/chemistry , Biomarkers/analysis , Early Diagnosis , BiopsyABSTRACT
Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut microbiome, the largest microbial reservoir in the human body, plays a significant role in this pathogenic process. Intestinal dysbiosis and disruption of the intestinal mucosal barrier are common after severe burn, leading to bacterial translocation to the bloodstream and other organs of the body, which is associated with many subsequent severe complications. The progression of some intestinal diseases can be improved by modulating the composition of gut microbiota and the levels of its metabolites, which also provides a promising direction for post-burn treatment. In this article, we summarised the studies describing changes in the gut microbiome after severe burn, as well as changes in the function of the intestinal mucosal barrier. Additionally, we presented the potential and challenges of microbial therapy, which may provide microbial therapy strategies for severe burn.
Subject(s)
Gastrointestinal Microbiome , Sepsis , Humans , Bacterial Translocation , Intestinal Mucosa , Sepsis/therapyABSTRACT
BACKGROUND: Early prediction of life-threatening malignant cerebral edema (MCE) after mechanical thrombectomy (MT) is of clinical importance. Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 are induced after acute ischemic stroke (AIS), the relationship between expressions of these molecules after MT and MCE as well as outcome in AIS patients have rarely been explored. METHODS: We retrospectively reviewed the data of all AIS patients with large-vessel occlusion in anterior circulation who underwent MT from our stroke centers. The serum levels of CAMs and KLF4 were determined at 12 h after MT. MCE was assessed on follow-up head computed tomography within 5 days after MT. RESULTS: Of 91 included patients, 18 (19.8 %) patients experienced MCE. Patients with MCE were more likely to have higher levels of E-selectin and inter-cellular adhesion molecule 1 (ICAM-1) than those without MCE (P < 0.05). More specifically, elevated E-selectin, but not of vascular cell adhesion molecule 1 (VCAM-1), ICAM-1 and KLF4, was significantly associated with MCE after adjusting for hypertension, admission NIHSS, Alberta Stroke Program Early CT Scores, serum glucose, collateral circulation and onset to recanalization time respectively (P < 0.05). ROC curve suggested that E-selectin had considerable discrimination to predict MCE (AUC=0.7, 95 % CI: 0.55-0.83). Moreover, after adjusting by confounders, serum levels of E-selectin and ICAM-1 were independently associated with 3-month outcome in AIS patients after MT (both P < 0.05). CONCLUSIONS: These data indicate that of three CAMs, serum E-selectin level early after MT is the best predictor for MCE and outcome in AIS.