Cell-free DNA: a promising biomarker in infectious diseases.

Infectious diseases pose serious threats to public health worldwide. Conventional diagnostic methods for infectious diseases often exhibit low sensitivity, invasiveness, and long turnaround times. User-friendly point-of-care tests are urgently needed for early diagnosis, treatment monitoring, and prognostic prediction of infectious diseases. Cell-free DNA (cfDNA), a promising non-invasive biomarker widely used in oncology and pregnancy, has shown great potential in clinical applications for diagnosing infectious diseases. Here, we discuss the most recent cfDNA research on infectious diseases from both the pathogen and host perspectives. We also discuss the technical challenges in this field and propose solutions to overcome them. Additionally, we provide an outlook on the potential of cfDNA as a diagnostic, treatment, and prognostic marker for infectious diseases.

The combination of tetramethylpyrazine and vitamin A acid in the treatment of skin photoaging by activating the HIF-1α pathway.

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. ß-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200µg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.

Advances in SIRT3 involvement in regulating autophagy-related mechanisms.

The silencing regulatory factor 2-like protein 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+) dependent deacetylase located primarily in the mitochondria. This protein plays an important role in oxidative stress, energy metabolism, and autophagy in multicellular organisms. Autophagy (macroautophagy) is primarily a cytoprotective mechanism necessary for intracellular homeostasis and the synthesis, degradation, and recycling of cellular products. Autophagy can influence the progression of several neural, cardiac, hepatic, and renal diseases and can also contribute to the development of fibrosis, diabetes, and many types of cancer. Recent studies have shown that SIRT3 has an important role in regulating autophagy. Therefore in this study, we aimed to perform a literature review to summarize the role of SIRT3 in the regulation of cellular autophagy. The findings of this study could be used to identify new drug targets for SIRT3-related diseases. Methods: A comprehensive literature review of the mechanism involved behind SIRT3 and autophagy-related diseases was performed. Relevant literature published in Pubmed and Web of Science up to July 2023 was identified using the keywords "silencing regulatory factor 2-like protein 3", "SIRT3" and "autophagy".

Lupeol improves bile acid metabolism and metabolic dysfunction-associated steatotic liver disease in mice via FXR signaling pathway and gut-liver axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a multifactorial and complex pathogenesis. Notably, the disorder of Bile acid (BA) metabolism and lipid metabolism-induced lipotoxicity are the main risk factors of MASLD. Lupeol, traditional regional medicine from Xinjiang, has a long history of use for its anti-inflammatory, anti-tumor, and immune-modulating properties. Recent research suggests its potential as a therapeutic option for MASLD due to its proposed binding capacity to the nuclear BA receptor, Farnesoid X receptor (FXR), hence could represent a therapeutic option for MASLD. In this study, a natural triterpenoid drug lupeol improved BA metabolism and MASLD in mice through the FXR signaling pathway and the gut-liver axis. Furthermore, lupeol effectively restored gut healthiness and improved intestinal immunity, barrier integrity, and inflammation, as indicated by the reconstructed gut flora. Compared with fenofibrate (Feno), lupeol treatment significantly reduced weight gain, fat deposition, and liver injury, decreased serum total cholesterol (TC) and triglyceride (TG) levels, and alleviated hepatic steatosis and liver inflammation. BA analysis showed that lupeol treatment accelerated BA efflux and decreased uptake of BA by increasing hepatic FXR and bile salt export pump (BSEP) expression. Gut microbiota alterations could be related to enhanced fecal BA excretion in lupeol-treated mice. Therefore, consumption of lupeol may prevent HFD-induced MASLD and BA accumulation, possibly via the FXR signaling pathway and regulating the gut microbiota.

Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy.

Background: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo. Methods: In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model. Results: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention. Conclusion: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.

PMBC: a manually curated database for prognostic markers of breast cancer.

Breast cancer is notorious for its high mortality and heterogeneity, resulting in different therapeutic responses. Classical biomarkers have been identified and successfully commercially applied to predict the outcome of breast cancer patients. Accumulating biomarkers, including non-coding RNAs, have been reported as prognostic markers for breast cancer with the development of sequencing techniques. However, there are currently no databases dedicated to the curation and characterization of prognostic markers for breast cancer. Therefore, we constructed a curated database for prognostic markers of breast cancer (PMBC). PMBC consists of 1070 markers covering mRNAs, lncRNAs, miRNAs and circRNAs. These markers are enriched in various cancer- and epithelial-related functions including mitogen-activated protein kinases signaling. We mapped the prognostic markers into the ceRNA network from starBase. The lncRNA NEAT1 competes with 11 RNAs, including lncRNAs and mRNAs. The majority of the ceRNAs in ABAT belong to pseudogenes. The topology analysis of the ceRNA network reveals that known prognostic RNAs have higher closeness than random. Among all the biomarkers, prognostic lncRNAs have a higher degree, while prognostic mRNAs have significantly higher closeness than random RNAs. These results indicate that the lncRNAs play important roles in maintaining the interactions between lncRNAs and their ceRNAs, which might be used as a characteristic to prioritize prognostic lncRNAs based on the ceRNA network. PMBC renders a user-friendly interface and provides detailed information about individual prognostic markers, which will facilitate the precision treatment of breast cancer. PMBC is available at the following URL: http://www.pmbreastcancer.com/.

Pan-cancer analysis of the prognostic and immunological role of FKBP4.

Objectives: Our previous studies revealed the significant roles of FK506-binding protein 4 (FKBP4) in tumorigenesis, however, there has been no pan-cancer analysis of FKBP4. Using bioinformatics, the current study reported the expression and prognostic role of FKBP4, and the correlation between FKBP4 and clinicopathological parameters, methylation, molecular network, immunological traits and drug sensitivity. Methods: RNA sequencing data, somatic mutation, and related clinical information were obtained from TCGA using UCSC Xena. The association between FKBP4 expression and clinical features was assessed using TISIDB. The relationships between FKBP4 expression and tumour stage, OS, DSS, DFS, and PFS were analysed using univariate cox regression analysis. The radar plots for TMB and MSI were obtained using "Fmsb" R package. UALCAN was used to explore the effect of FKBP4 methylation on tumour and normal samples. CBioportal was used to analyse copy number mutations in FKBP4 Gene expression and drug sensitivity data were downloaded from the CellMiner database. GO analysis was performed for the high and the low expression of FKBP4 compared with the median level of FKBP4 using clusterProfiler4.0. Results: FKBP4 expression is significantly upregulated in various types of cancers. Cox regression analysis showed that high FKBP4 levels were correlated with poor OS, DSS, DFS, and PFS in most patients with cancer. Methylation of FKBP4 DNA was upregulated in most cancers, and FKBP4 expression is positively associated with transmethylase expression. FKBP4 and its copy were significantly associated with the expression of immune-infiltrating cells, immune checkpoint genes, immune modulators, TMB, MMR, and MSI. FKBP4 expression levels significantly correlated with 16 different drug sensitivities (all p < 0.05). Conclusions: Our pan-cancer bioinformatic analysis revealed a potential mechanism underlying the effects of FKBP4 on the prognosis and progression of various cancers.

Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.

Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

A Novel CaCu-Metal-Organic-Framework Based Multimodal Treatment Platform for Enhanced Synergistic Therapy of Hepatocellular Carcinoma.

Metal ions have attracted a lot of interest in antitumor therapy due to their unique mechanism of action. However, multiple death mechanisms associate with metal ions to synergistic antitumors have few studies mainly due to the serious challenges in designing and building metal-associated multimodal treatment platforms. Hence, a series of glutathione-activatable CaCu-based metal-organic-frameworks loaded with doxorubicin and ovalbumin are successfully designed and synthesized with an "all in one" strategy, which is modified by galactosamine-linked hyaluronic acid to prepare multimodal treatment platform (SCC/DOX@OVA-HG) for targeted delivery and synergistic antitumor therapy. SCC/DOX@OVA-HG can be rapidly degraded by the overexpressed glutathione and then releases the "cargoes" in the tumor microenvironment. The released Cu+ efficiently catalyzes H2O2 to produce highly toxic ROS for CDT, and the up-regulation of calcium ion concentration in tumor cells induced by the released Ca2+ enables calcium overload therapy, which synergically enhances the metal-related death pattern. Meanwhile, OVA combined with Ca2+/Cu2+ further activates macrophages into an M1-like phenotype to accelerate tumor cell death through immunotherapy. Besides, the released DOX can also insert into the DNA double helix for chemotherapy. Consequently, the developed SCC/DOX@OVA-HG reveals significantly improved antitumor efficacy through a multimodal synergistic therapy of chemotherapy, chemodynamic therapy, calcium overload, and immunotherapy.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

Tuberculosis-targeted next-generation sequencing and machine learning: An ultrasensitive diagnostic strategy for paucibacillary pulmonary tuberculosis and tuberculous meningitis.

BACKGROUND: Existing diagnostic approaches for paucibacillary tuberculosis (TB) are limited by the low sensitivity of testing methods and difficulty in obtaining suitable samples. METHODS: An ultrasensitive TB diagnostic strategy was established, integrating efficient and specific TB targeted next-generation sequencing and machine learning models, and validated in clinical cohorts to test plasma cfDNA, cerebrospinal fluid (CSF) DNA collected from tuberculous meningitis (TBM) and pediatric pulmonary TB (PPTB) patients. RESULTS: In the detection of 227 samples, application of the specific thresholds of CSF DNA (AUC = 0.974) and plasma cfDNA (AUC = 0.908) yielded sensitivity of 97.01 % and the specificity of 95.65 % in CSF samples and sensitivity of 82.61 % and specificity of 86.36 % in plasma samples, respectively. In the analysis of 44 paired samples from TBM patients, our strategy had a high concordance of 90.91 % (40/44) in plasma cfDNA and CSF DNA with both sensitivity of 95.45 % (42/44). In the PPTB patient, the sensitivity of the TB diagnostic strategy yielded higher sensitivity on plasma specimen than Xpert assay on gastric lavage (28.57 % VS. 15.38 %). CONCLUSIONS: Our TB diagnostic strategy provides greater detection sensitivity for paucibacillary TB, while plasma cfDNA as an easily collected specimen, could be an appropriate sample type for PTB and TBM diagnosis.

Hollow MIL-125 Nanoparticles Loading Doxorubicin Prodrug and 3-Methyladenine for Reversal of Tumor Multidrug Resistance.

Multidrug resistance (MDR) is a key factor in chemotherapy failure and tumor recurrence. The inhibition of drug efflux and autophagy play important roles in MDR therapy. Herein, a multifunctional delivery system (HA-MIL-125@DVMA) was prepared for synergistically reverse tumor MDR. Tumor-targeted hollow MIL-125-Ti nanoparticles were used to load the doxorubicin-vitamin E succinate (DV) prodrug and 3-methyladenine (3-MA) to enhance reverse MDR effects. The pH-sensitive DV can kill tumor cells and inhibit P-gp-mediated drug efflux, and 3-MA can inhibit autophagy. HA-MIL-125@DVMA had uniformly distributed particle size and high drug-load content. The nanoparticles could effectively release the drugs into tumor microenvironment due to the rapid hydrazone bond-breaking under low pH conditions, resulting in a high cumulative release rate. In in vitro cellular experiments, the accumulation of HA-MIL-125@DVMA and HA-MIL-125@DV in MCF-7/ADR cells was significantly higher than that in the control groups. Moreover, the nanoparticles significantly inhibited drug efflux in the cells, ensuring the accumulation of the drugs in cell cytoplasm and causing drug-resistant cells' death. Importantly, HA-MIL-125@DVMA effectively inhibited tumor growth without changes in body weight in tumor-bearing mice. In summary, the combination of the acid-sensitive prodrug DV and autophagy inhibitor 3-MA in a HA-MIL-125 nanocarrier can enhance the antitumor effect and reverse tumor MDR.

Waterborne copper exposure decreases fish growth and survival by promoting gills and liver impairments in largemouth bass (Micropterus salmoides).

The study aimed to investigate the effect of Cu exposure (0, 51.3, 164, 513, 1,640, and 5,130 µg/L) on fish growth performance, histology, oxidative stress, inflammation, and apoptosis in largemouth bass (Micropterus salmoides) juveniles. 270 fish (2.69 ± 0.02 g) were randomly divided into 6 groups of tanks for 4 weeks with each group comprising three replicate tanks. The results showed that fish exposed to 1,640 and 5,130 µg/L Cu exhibited a significant reduction in fish growth and survival rate (P < 0.05). Compared to the control, the fish at and above 513 µg/L Cu demonstrated histopathological damages in the gills and liver, such as shorter primary and secondary lamellae, smaller hepatocyte nuclei, and an increase in the number of necrotic cells in the liver. Compared to the control, fish at and above 1,640 µg/L Cu had a significantly higher malondialdehyde content and lower activity levels of total superoxide dismutase, glutathione peroxidase, and catalase in the gills and liver (P < 0.05). Furthermore, high concentrations of Cu (1,640 and 5,130 µg/L) significantly increased hepatic inflammation by upregulating interleukin-1ß and tumor necrosis factor α expression and hepatic apoptosis by increasing cysteinyl aspartate specific protease 3 (caspase-3) and caspase-9 expression (P < 0.05). Pearson correlation analysis showed that fish growth and survival positively correlated with histological and antioxidant defense parameters, and negatively correlated with oxidative stress parameters, hepatic inflammation, and hepatic apoptosis. Taken together, these results suggest that high levels of waterborne Cu can induce growth retardation and mortality by damaging the liver and gill health.

Application of tangent-arc technology for deep inspiration breath-hold radiotherapy in left-sided breast cancer.

Objective: To explore the advantages of dosimetry and the treatment efficiency of tangent-arc technology in deep inspiration breath-hold radiotherapy for breast cancer. Methods: Forty patients with left-sided breast cancer who were treated in our hospital from May 2020 to June 2021 were randomly selected and divided into two groups. The first group's plan was a continuous semi-arc that started at 145° ( ± 5°) and stopped at 325° ( ± 5°). The other group's plan, defined as the tangent-arc plan, had two arcs: the first arc started at 145° ( ± 5°) and stopped at 85° ( ± 5°), and the second arc started at 25° ( ± 5°) and stopped at 325° ( ± 5°). We compared the target dose, dose in organs at risk (OARs), and treatment time between the two groups. Results: The target dose was similar between the continuous semiarc and tangent-arc groups. The V5 of the right lung was significantly different between the two groups (Dif 5.52, 95% confidence interval 1.92-9.13, t=3.10, P=0.004), with the patients in the continuous semi-arc and tangent-arc groups having lung V5 values of (9.16 ± 1.62)%, and (3.64 ± 0.73)%, respectively. The maximum dose to the spinal cord was (1835.88 ± 222.17) cGy in the continuous semi-arc group and (599.42 ± 153.91) cGy in the tangent-arc group, yielding a significant difference between the two groups (Dif 1236.46, 95% confidence interval 689.32-1783.6, t=4.57, P<0.001). The treatment times was (311.70 ± 60.45) s for patients in the continuous semi-arc group and (254.66 ± 40.73) s for patients in the tangent-arc group, and there was a significant difference in the mean number of treatment times between the two groups (Dif 57.04, 95% confidence interval 24.05-90.03, t=3.5, P=0.001). Conclusion: Both the continuous semi-arc and tangent-arc plans met the clinical prescription dose requirements. The OARs received less radiation with the tangent-arc plan than the continuous semi-arc plan, especially for the lung (measured as V5) and the spinal cord (measured as the maximum dose). Tangent-arc plan took significantly less time than the continuous semi-arc, which can greatly improve treatment efficiency. Therefore, tangent-arc plans are superior continuous semi-arc plans for all cases.

Unraveling the Antioxidant Activity of 2R,3R-dihydroquercetin.

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in 'biotargeting' quercetin.

GSH-Activatable Metal-Phenolic Networks for Photothermal-Enhanced Chemotherapy and Chemodynamic Therapy.

Chemotherapy (CT) plays an important role in the antitumor process, but the unsatisfactory therapeutic efficacy and the obvious toxic side effects of CT seriously restrict its application. To overcome the limitations of CT, the strategy of chemotherapy enhanced by chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising approach to improve the anticancer effect. Herein, a novel GSH-activatable Cu2+-Quercetin network (QC) was synthesized via a convenient strategy to load Au nanoparticles (NPs) and DOX, named QCDA, for the synergistic therapy of CT/CDT/PTT. The results showed that QCDA exhibited GSH-sensitive degradation and "cargos" release in cancer cells, and then PTT and CDT caused by Au NPs and Cu+ significantly enhanced the CT effect of DOX and Quercetin on anticancer. More importantly, the PTT and depleted GSH accelerated the Fenton-like ionization process resulting in facilitating the CDT efficiency. Collectively, the multi-mode synergistic strategy of CT/CDT/PTT, which showed an excellent therapeutic effect, maybe a potential therapeutic pathway for anticancer.

A2b and A3 adenosine receptors may act as promotive and prognostic factors in oral squamous cell carcinoma.

This study aimed to examine the expression and potential effects of adenosine receptors in oral squamous cell carcinoma (OSCC). Data on mRNA expression of adenosine receptors in OSCC samples were collected from The Cancer Genome Atlas database. Adenosine-regulated signaling pathways and biological processes were investigated via immune cell infiltration analysis, bioinformatics analysis, and immunohistochemistry. Overexpression of A2bR and A3R was significantly correlated with the prognosis of OSCC (P < 0.05). A3R expression in OSCC patients was significantly and positively correlated with the infiltration of six types of immune cells: B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells. A2bR expression weakly and negatively correlated with B-cell infiltration only. The expression of A2bR in OSCC was positively correlated with E-cadherin and PCNA, while the expression of A3R was positively correlated with that of cleaved caspase-3. Within the limitations of the study it seems that the overexpression of A2bR and A3R results in the poor prognosis of OSCC, suggesting that A2bR promotes cell proliferation in OSCC, while A3R may be involved in OSCC progression by regulating tumor cell apoptosis and immune microenvironment.

Sodium alginate emulsion loaded with linalool: Preparation, characterization and antibacterial mechanism against Shigella sonnei.

This study aimed to prepare sodium alginate-linalool emulsion (SA-LE) to overcome the low solubility of linalool and explore its inhibitory activity against Shigella sonnei. The results indicated that linalool significantly reduced the interfacial tension between SA and oil phase (p < 0.05). Droplet sizes of fresh emulsions were uniform with sizes from 2.54 to 2.58 µm. The ζ-potential was between -23.94 and -25.03 mV, and the viscosity distribution was 973.62 to 981.03 mPa·s at pH 5-8 (near neutral pH) without significant difference. In addition, linalool could be effectively released from SA-LE in accordance with the Peppas-Sahlin model, mainly described by Fickian diffusion. In particular, SA-LE can inhibit S. sonnei with a minimum inhibitory concentration of 3 mL/L, which was lower than free linalool. The mechanism can be described as damaging the membrane structure and inhibiting respiratory metabolism accompanied by oxidative stress based on FESEM, SDH activity, ATP and ROS content. These results suggest that SA is an effective encapsulation strategy to enhance the stability of linalool and its inhibitory effect on S. sonnei at near neutral pH. Moreover, the prepared SA-LE has the potential to be developed as a natural antibacterial agent to address the growing food safety challenges.

Efficient pH-Responsive Nano-Drug Delivery System Based on Dynamic Boronic Acid/Ester Transformation.

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.