Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination.

Immunogenic cell death (ICD) is a stress-driven form of regulated cell death (RCD) in which dying tumor cells' specific signaling pathways are activated to release damage-associated molecular patterns (DAMPs), leading to the robust anti-tumor immune response as well as a reversal of the tumor immune microenvironment from "cold" to "hot". Chimeric antigen receptor (CAR)-T cell therapy, as a landmark in anti-tumor immunotherapy, plays a formidable role in hematologic malignancies but falls short in solid tumors. The Gordian knot of CAR-T cells for solid tumors includes but is not limited to, tumor antigen heterogeneity or absence, physical and immune barriers of tumors. The combination of ICD induction therapy and CAR-T cell immunotherapy is expected to promote the intensive use of CAR-T cell in solid tumors. In this review, we summarize the characteristics of ICD, stress-responsive mechanism, and the synergistic effect of various ICD-based therapies with CAR-T cells to effectively improve anti-tumor capacity.

The underlying mechanism of chimeric antigen receptor (CAR)-T cell therapy triggering secondary T-cell cancers: Mystery of the Sphinx?

The U.S. Food and Drug Administration (FDA) has reported cases of T-cell malignancies, including CAR-positive lymphomas, in patients receiving B cell maturation antigen (BCMA)- or CD19-targeted autologous CAR-T cell immunotherapy. These reports were derived from clinical trials and/or post-marketing adverse event data. This finding has attracted widespread attention. Therefore, it is essential to explore the potential mechanisms by which chimeric antigen receptor (CAR)-T cell therapy triggers secondary T-cell cancers to further guarantee the safety of CAR-T cell therapy.

Molecular subtypes of ischemic heart disease based on circadian rhythm.

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.

Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Oxidized mitochondrial DNA activates the cGAS-STING pathway in the neuronal intrinsic immune system after brain ischemia-reperfusion injury.

In the context of stroke and revascularization therapy, brain ischemia-reperfusion injury is a significant challenge that leads to oxidative stress and inflammation. Central to the cell's intrinsic immunity is the cGAS-STING pathway, which is typically activated by unusual DNA structures. The involvement of oxidized mitochondrial DNA (ox-mtDNA)-an oxidative stress byproduct-in this type of neurological damage has not been fully explored. This study is among the first to examine the effect of ox-mtDNA on the innate immunity of neurons following ischemia-reperfusion injury. Using a rat model of transient middle cerebral artery occlusion and a cellular model of oxygen-glucose deprivation/reoxygenation, we have discovered that ox-mtDNA activates the cGAS-STING pathway in neurons. Importantly, pharmacologically limiting the release of ox-mtDNA into the cytoplasm reduces inflammation and improves neurological functions. Our findings suggest that targeting ox-mtDNA release may be a valuable strategy to attenuate brain ischemia-reperfusion injury following revascularization therapy for acute ischemic stroke.

Metabolomic analysis revealed the edible and extended-application potential of specific Polygonum multiflorum tissues.

The diverse applications of various tissues of Polygonum Multiflorum (PM) encompass the use of its leaf and bud as tea and vegetables, as well as the utilization of its expanded root tubers and caulis as medicinal substances. However, previous studies in the field of metabolomics have primarily focused on the medicinal properties of PM. In order to investigate the potential for broader applications of other tissues within PM, a metabolomic analysis was conducted for the first time using UPLC-Q-TOF-MS/MS on 15 fresh PM tissues. A total of 231 compounds, including newly discovered compounds such as torosachrysone and dihydro-trihydroxystilbene acid derivatives, were identified within PM. Through clustering analysis, the PM tissues were categorized into edible and medicinal parts, with edible tissues exhibiting higher levels of phenolic acids, organic acids, and flavonoids, while the accumulation of quinones, dianthrones, stilbenes, and xanthones was observed in medicinal tissues. Comparative analysis demonstrated the potential application of discarded tissues, such as unexpanded root tuber (an industrial alternative to expanded root tuber) and young caulis (with edible potential). Moreover, the quantification of representative metabolites indicated that flowers and buds contained significant amounts of flavonoids or phenolic acids, suggesting their potential as functional food. Additionally, the edible portion of PM exhibited a high content of quercitrin, ranging from 0.59 to 10.37 mg/g. These findings serve as a valuable point of reference for the expanded utilization of PM tissues, thereby mitigating resource waste in this plant.

Blocking cerebral lymphatic system reduces central and peripheral inflammatory response in ischemic stroke.

Reduced blood supply to the brain activates the intracranial inflammatory response, a key contributor to secondary brain damage in ischemic stroke. Post-stroke, activation of peripheral immune cells leads to systemic inflammatory responses. Usingin vivo approaches, we investigated meningeal lymphatics' role in central immune cell infiltration and peripheral immune cell activation. The bilateral deep cervical lymph nodes (dCLNs) were removed 7 days before right middle cerebral artery occlusion in Sprague Dawley (SD) rats. At 3, 24, and 72 h post-intervention, brain immune cell infiltration and microglial and astrocyte activation were measured, while immune cells were classified in the spleen and blood. Inflammatory factor levels in peripheral blood were analyzed. Simultaneously, reverse verification was conducted by injecting AAV-vascular endothelial growth factor C (AAV-VEGFC) adenovirus into the lateral ventricle 14 days before middle cerebral artery occlusion (MCAO) induction to enhance meningeal lymph function. Blocking meningeal LVs in MCAO rats significantly reduced infarct area and infiltration, and inhibited microglia and pro-inflammatory astrocytes activation. After removing dCLNs, CD4+ T lymphocytes, CD8+ T lymphocytes, B lymphocytes, macrophages, and neutrophils in the spleen and blood of MCAO rats decreased significantly at different time points. The levels of inflammatory factors IL-6, IL-10, IL-1ß, and TNF-α in plasma decreased significantly. Tests confirmed the results, and AAV-VEGFC-induced MCAO rats provided reverse validation.

Hit-and-run vaccine system that overcomes limited neoantigen epitopes for efficient broad antitumor response.

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies. However, identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines. Herein, we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens". This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens. We demonstrated that a poly(2-oxazoline)s (POx) conjugated with OVA257-264 peptide through a matrix metalloprotease 2 (MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo. Then, a POx-based nanovaccine containing OVA257-264 peptides to elicit OVA-specific T cell responses was designed. In combination with this hit-and-run vaccine system, an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression. This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

Combining Cd and Pb isotope analyses for heavy metal source apportionment in facility agricultural soils around typical urban and industrial areas.

Facility agriculture enhances food production capabilities. However, concerns persist regarding heavy metal accumulation resulting from extensive operation of this type of farming. This study integrated the total content, five fractions, and isotope composition of Cd and Pb in intensively farmed soils in regions characterized by industrialization (Shaoguan, SG) and urbanization (Guangzhou, GZ), to assess the sources and mechanisms causing metals accumulation. We found significantly more severe Cd/Pb accumulation and potential mobility in SG than GZ. Cd displayed higher accumulation levels and potential mobility than Pb. The distinct isotopic signals in SG (-0.54 to 0.47‰ for δ114/110Cd and 1.1755 to 1.1867 for 206Pb/207Pb) and GZ (-0.86 to 0.12‰ for δ114/110Cd and 1.1914 to 1.2012 for 206Pb/207Pb) indicated significant differences in Cd/Pb sources. The Bayesian model revealed that industrial activities and related transportation accounted for over 40% and approximately 30%, respectively, of the average contributions of Cd/Pb in SG. While urban-related (26.6%) and agricultural-related (26.3%) activities primarily contributed to Cd in GZ. The integration of δ114/110Cd and 208Pb/206Pb has further enhanced the regional contrast in sources. The present study established a comprehensive tracing system for Cd-Pb, providing crucial insights into the accumulation and distribution of these metals in facility agricultural soils.

Omics-based molecular classifications empowering in precision oncology.

BACKGROUND: In the past decades, cancer enigmatical heterogeneity at distinct expression levels could interpret disparities in therapeutic response and prognosis. It built hindrances to precision medicine, a tactic to tailor customized treatment informed by the tumors' molecular profile. Single-omics analysis dissected the biological features associated with carcinogenesis to some extent but still failed to revolutionize cancer treatment as expected. Integrated omics analysis incorporated tumor biological networks from diverse layers and deciphered a holistic overview of cancer behaviors, yielding precise molecular classification to facilitate the evolution and refinement of precision medicine. CONCLUSION: This review outlined the biomarkers at multiple expression layers to tutor molecular classification and pinpoint tumor diagnosis, and explored the paradigm shift in precision therapy: from single- to multi-omics-based subtyping to optimize therapeutic regimens. Ultimately, we firmly believe that by parsing molecular characteristics, omics-based typing will be a powerful assistant for precision oncology.

Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics. RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate. CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.

The triterpenoid saponin content difference is associated with the two type oxidosqualene cyclase gene copy numbers of Pulsatilla chinensis and Pulsatilla cernua.

Pulsatilla chinensis is an important medicinal herb, its dried radix is used to treat the inflammation since ancient China. Triterpenoid saponins are proved to be the main active compounds of Pulsatilla genus. The triterpenoid saponin contents vary widely in different Pulsatilla species. But no enzyme involved in the triterpenoid saponin biosynthetic pathway was identified in Pulsitilla genus. This seriously limits the explanation of the triterpene content difference of Pulsatilla species. In this article, we obtained two oxidosqualene cyclase (OSC) genes from P. chinensis and P. cernua by touchdown PCR and anchored PCR. These two OSCs converted 2,3-oxidosqualene into different triterpenoids. The OSC from P. cernua is a monofunctional enzyme for ß-amyrin synthesis, while the OSC from P. chinensis is a multifunctional enzyme for lupeol and ß-amyrin synthesis, and the lupeol is the main product. Then we identified the 260th amino acid residue was the key site for the product difference by gene fusion and site-directed mutant technology. When the 260th amino acid residue was tryptophan (W260) and phenylalanine (F260), the main catalysate was ß-amyrin and lupeol, respectively. Then we found that the expression of these two genes was strongly correlated with the lupeol-type and ß-amyrin-type triterpenoid contents in P. cernua and P. chinensis. Finally, we found the gene copy number difference of these two genotypes leaded to the triterpenoid diversity in P. cernua and P. chinensis. This study provides useful information for the molecular breeding and quality improvement of P. chinensis and a molecular marker to identify the P. chinensis decoction pieces.

Rapid quality evaluation of four kinds of Polygoni Multiflori Radix Praeparata by electronic eye combined with chemometrics.

INTRODUCTION: Polygonum multiflorum Thunb., a widely used herbal medicine, has trouble with the hepatic adverse effect. Processing is an effective method to increase potency and reduce the adverse effects of herbal medicines. Polygoni Multiflori Radix Praeparata (PMRP), the decoction pieces processed from raw material, is widely consumed in clinical practice in many countries. The quality control of PMRP has attracted more and more attention worldwide. OBJECTIVE: A simple and rapid quality evaluation method using an electronic eye (E-eye) combined with chemometrics was proposed for controlling the quality of PMRP. MATERIALS AND METHODS: The semi-quantitative and quantitative data of 105 major components in 128 batches of PMRP samples obtained by three different analysis instruments were fused to investigate the correlation with the dynamic exterior colour determined by E-eye. The correlation between exterior colour and chemical fusion dataset was investigated by orthogonal partial least squares discriminant analysis (OPLS-DA) and partial least squares regression (PLSR). According to the results of correlation analysis, the color parameters of high-quality PMRP was set. RESULTS: Correlation studies by chemometrics revealed that the exterior colour depth was significantly correlated with 32 components [variable importance in the projection (VIP) > 1.0, p < 0.05]. The colour parameter of E * ab located in the range of 46.69-51.66 can be used easily, rapidly, and in an environment-friendly way to determine whether the PMRP sample has reached sufficient processing time with good quality. CONCLUSION: This study adds some scientific information to our understanding of traditional medicine while contributing an alternative method for assessing the quality of other decoction pieces.

Immune-related interaction perturbation networks unravel biological peculiars and clinical significance of glioblastoma.

The immune system is an interacting network of plentiful molecules that could better characterize the relationship between immunity and cancer. This study aims to investigate the behavioral patterns of immune-related interaction perturbation networks in glioblastoma. An immune-related interaction-perturbation framework was introduced to characterize four heterogeneous subtypes using RNA-seq data of TCGA/CGGA glioblastoma tissues and GTEx normal brain tissues. The stability and robustness of the four subtypes were validated in public datasets and our in-house cohort. In the four subtypes, C1 was an inflammatory subtype with high immune infiltration, low tumor purity, and potential response to immunotherapy; C2, an invasive subtype, was featured with dismal prognosis, telomerase reverse transcriptase promoter mutations, moderate levels of immunity, and stromal constituents, as well as sensitivity to receptor tyrosine kinase signaling inhibitors; C3 was a proliferative subtype with high tumor purity, immune-desert microenvironment, sensitivity to phosphatidylinositol 3'-kinase signaling inhibitor and DNA replication inhibitors, and potential resistance to immunotherapy; C4, a synaptogenesis subtype with the best prognosis, exhibited high synaptogenesis-related gene expression, prevalent isocitrate dehydrogenase mutations, and potential sensitivity to radiotherapy and chemotherapy. Overall, this study provided an attractive platform from the perspective of immune-related interaction perturbation networks, which might advance the tailored management of glioblastoma.

Metabolic profile and dynamic characteristic of rhubarb during the vitro biotransformation by human gut microbiota.

Rhubarb is a popular food in the world with laxative effects and steamed pieces of rhubarb (SP) have been widely applied to treatment of constipation in China due to its safety and effectiveness. In the study, metabolism in vitro was conducted to study influence of gut microbiota between raw pieces of rhubarb (RP) and SP. The results showed obvious classifications in metabolic profile between RP and SP were revealed by chemometric analysis, and prompted gut microbiota affected metabolism of rhubarb. Furthermore, 16 characteristic components were identified to distinguish the differences in metabolism. Finally, quantitative analysis of 14 components were verified the regulation of gut microbiota on rhubarb and discovered concentration of components affected the rate of metabolism. The study indicated regulation by gut microbiota could be probably responsible for differences of laxative effects between RP and SP, providing new perspective for exploring mechanisms of effectiveness in clinical application for SP.

Effect of genetically modified maize expressing the Cry1Ab and EPSPS proteins on growth, development, and gut bacterial diversity of the non-target arthropod Locusta migratoria.

The widespread cultivation of genetically modified (GM) crops has raised concerns for their safety. Here, we evaluated the effects of a GM maize variety expressing the Cry1Ab (14.76 ± 0.87 µg/g FW) and EPSPS proteins (191.55 ± 15.69 µg/g FW) on the life-history traits and gut bacterial community of a non-target arthropod, Locusta migratoria, in the laboratory. We found that GM maize had no significant effect on the survival or body weight of different development stages of L. migratoria. The midgut and hindgut bacterial diversities and compositions were determined using high-throughput sequencing targeting the V3-V4 regions of the 16S rRNA. No significant changes were found in the species diversity or abundance between insects in the GM-fed treatment and the non-GM control. Furthermore, the concentration of Cry1Ab and EPSPS in the gut was determined after digestion of GM maize. Results showed that the contents of Cry1Ab/EPSPS rapidly decreased and were hard to detect after 72 h. Based on the parameters assessed, we can conclude that the GM maize variety examined has no significant adverse effect on L. migratoria.

Mannan-decorated pathogen-like polymeric nanoparticles as nanovaccine carriers for eliciting superior anticancer immunity.

Using nanotechnology for cancer vaccine design holds great promise because of the intrinsic feature of nanoparticles in being captured by antigen-presenting cells (APCs). However, there are still obstacles in current nanovaccine systems in achieving efficient tumor therapeutic effects, which could partially be attributed to the unsatisfactory vaccine carrier design. Herein, we report a mannan-decorated pathogen-like polymeric nanoparticle as a protein vaccine carrier for eliciting robust anticancer immunity. This nanovaccine was constructed as a core-shell structure with mannan as the shell, polylactic acid-polyethylenimine (PLA-PEI) assembled nanoparticle as the core, and protein antigens and Toll-like receptor 9 (TLR9) agonist CpG absorbed onto the PLA-PEI core via electrostatic interactions. Compared to other hydrophilic materials, mannan decoration could greatly enhance the lymph node draining ability of the nanovaccine and promote the capturing by the CD8+ dendritic cells (DCs) in the lymph node, while PLA-PEI as the inner core could enhance antigen endosome escape thus promoting the antigen cross-presentation. In addition, mannan itself as a TLR4 agonist could synergize with CpG for maximally activating the DCs. Excitingly, we observed in several murine tumor models that using this nanovaccine alone could elicit robust immune response in vivo and result in superior anti-tumor effects with 50% of mice completely cured. This study strongly evidenced that mannan decoration and a rationally designed nanovaccine system could be quite robust in tumor vaccine therapy.

A Minimalist Binary Vaccine Carrier for Personalized Postoperative Cancer Vaccine Therapy.

In recent years, significant evolutions have been made in applying nanotechnologies for prophylactic and therapeutic cancer vaccine design. However, the clinical translation of nanovaccines is still limited owing to their complicated compositions and difficulties in the spatiotemporal coordination of antigen-presenting cell activation and antigen cross-presentation. Herein, a minimalist binary nanovaccine (BiVax) is designed that integrates innate stimulating activity into the carrier to elicit robust antitumor immunity. The authors started by making a series of azole molecules end-capped polyethylenimine (PEI-M), and were surprised to find that over 60% of the PEI-M polymers have innate stimulating activity via activation of the stimulator of interferon genes pathway. PEI-4BImi, a PEI-M obtained from a series of polymers, elicits robust antitumor immune responses when used as a subcutaneously injected nanovaccine by simply mixing with ovalbumin antigens, and this BiVax system performs much better than the traditional ternary vaccine system, as well as, commercialized aluminum-containing adjuvants. This system also enables the fast preparation of personalized BiVax by compositing PEI-4BImi with autologous tumor cell membrane protein antigens, and a 60% postoperative cure rate is observed when combined with immune checkpoint inhibitors.

Simultaneous quantification of anthraquinone glycosides, aglycones, and glucuronic acid metabolites in rat plasma and tissues after oral administration of raw and steamed rhubarb in blood stasis rats by UHPLC-MS/MS.

Rhubarb is a widely used herbal medicine. To achieve different effects, rhubarb is usually steamed with rice wine (steamed rhubarb). This steaming treatment increases the blood-activating and stasis-removing effects of rhubarb. A specific and accurate ultra high performance liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of anthraquinone glycosides, aglycones, and glucuronic acid metabolites in plasma and tissues after administration of raw rhubarb and steamed rhubarb in blood stasis rats. Chromatographic separation was performed on ACQUITY UPLC BEH Shield RP 18 column using the mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Satisfactory linearity, precision, accuracy, extraction recovery, and matrix effect have been achieved. From pharmacokinetic study, it showed that glucuronic acid metabolites were found abundantly in plasma as bioactive components. The lower area under concentration-time curve, maximum concentration, and higher apparent volume of distribution (P < 0.01), body clearance (P < 0.01) values in steamed rhubarb showed that most components of steamed rhubarb have lower bioavailability in plasma compared with raw rhubarb. But it found these components were mainly distributed in spleen and liver with large blood flow and perfusion rates. The pharmacokinetics and tissue distribution studies of anthraquinone components will provide helpful information for clinical application of steamed rhubarb and raw rhubarb.

A simple and general strategy for postsurgical personalized cancer vaccine therapy based on an injectable dynamic covalent hydrogel.

Cancer vaccines artificially stimulate the immune system against cancer and are considered the most promising treatment of cancer. However, the current progress in vaccine research against cancer is still limited and slow, partially due to the difficulties in identifying and obtaining tumor-specific antigens. Considering surgery as the first choice for tumor treatment in most cases, the authors evaluated whether the resected tumor can be directly used as a source of tumor antigens for designing personalized cancer vaccines. Based on this idea, herein, the authors report a dynamic covalent hydrogel-based vaccine (DCHVax) for personalized postsurgical management of tumors. The study uses proteins extracted from the resected tumor as antigens, CpG as the adjuvant, and a multi-armed poly(ethylene glycol) (8-arm PEG)/oxidized dextran (ODEX) dynamically cross-linked hydrogel as the matrix. Subcutaneous injection of DCHVax recruits dendritic cells to the matrix in situ and elicits robust tumor-specific immune responses. Thus, it effectively inhibits the postoperative growth of the residual tumor in several murine tumor models. This simple and personalized method to develop cancer vaccines may be promising in developing clinically relevant strategies for postoperative cancer treatment.