Abdominal pregnancy: a case report and review of 17 cases.

PURPOSE: To analyze the clinical characteristics of abdominal pregnancy, and to explore the diagnosis and prognosis of different treatment methods. METHODS: The cases of patients with abdominal pregnancy admitted to Peking Union Medical College Hospital between January 1, 1989 and January 1, 2021, were analyzed retrospectively. RESULTS: The median age of 17 patients was 34 years (22-42 years); the median gestational duration was 57 days (from 41 days to 32 weeks). Among all 17 patients, 15 (88.24%) presented with abdominal pain. The implantation sites of the gestational sac included the bladder peritoneal reflection, anterior wall of the rectum, omentum, serous membrane of the uterus, and inside or on the surface of uterosacral ligament. In all, only 29.41% cases (5/17) were diagnosed before surgery. All 17 patients were treated via surgery. Further, 58.82% (10/17) patients recovered without complications, 29.41% (5/17) developed fever, 5.88% (1/17) underwent reoperation because of intra-abdominal bleeding, and 5.88% (1/17) developed double lower limb venous thrombosis. All 17 patients survived. CONCLUSION: The preoperative diagnosis rate of abdominal pregnancy is low. Planting sites in the pelvic peritoneum and pelvic organs are more common than the others. Laparoscopic surgery in the first trimester of pregnancy can achieve better therapeutic effects. However, the blood supply of the placenta should be fully evaluated before surgery. When it is expected that attempts to remove the placenta will cause fatal bleeding, the placenta can be left in place, but long-term close follow-up should be paid attention to.

Dual-Loaded Liposomes Tagged with Hyaluronic Acid Have Synergistic Effects in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most lethal subtypes of breast cancer. Although chemotherapy is considered the most effective strategy for TNBC, most chemotherapeutics in current use are cytotoxic, meaning they target antiproliferative activity but do not inhibit tumor cell metastasis. Here, a TNBC-specific targeted liposomal formulation of epalrestat (EPS) and doxorubicin (DOX) with synergistic effects on both tumor cell proliferation and metastasis is described. These liposomes are biocompatible and effectively target tumor cells owing to hyaluronic acid (HA) modification on their surface. This active targeting, mediated by CD44-HA interaction, allows DOX and EPS to be delivered simultaneously to tumor cells in vivo, where they suppress not only TNBC tumor growth and the epithelial-mesenchymal transition, but also cancer stem cells, which collectively suppress tumor growth and metastasis of TNBC and may also act to prevent relapse of TNBC.

Predicting MCI progression with FDG-PET and cognitive scores: a longitudinal study.

BACKGROUND: Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Studies on MCI progression are important for Alzheimer's disease (AD) prevention. 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been proven to be a powerful tool for measuring cerebral glucose metabolism. In this study, we proposed a classification framework for MCI prediction with both baseline and multiple follow-up FDG-PET scans as well as cognitive scores of 33 progressive MCI (pMCI) patients and 46 stable MCI (sMCI) patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHOD: First, PET images were normalized using the Yakushev normalization procedure and registered to the Brainnetome Atlas (BNA). The average metabolic intensities of brain regions were defined as static features. Dynamic features were the intensity variation between baseline and the other three time points and change ratios with the intensity obtained at baseline considered as reference. Mini-mental State Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive section (ADAS-cog) scores of each time point were collected as cognitive features. And F-score was applied for feature selection. Finally, support vector machine (SVM) with radial basis function (RBF) kernel was used for the three above features. RESULTS: Dynamic features showed the best classification performance in accuracy of 88.61% than static features (accuracy of 78.48%). And the combination of cognitive features and dynamic features improved the classification performance in specificity of 95.65% and Area Under Curve (AUC) of 0.9308. CONCLUSION: Our results reported that dynamic features are more representative in longitudinal research for MCI prediction work. And dynamic features and cognitive scores complementarily enhance the classification performance in specificity and AUC. These findings may predict the disease course and clinical changes in individuals with mild cognitive impairment.

Antibacterial effects of a polypeptide-enriched extract of Rana chensinensis via the regulation of energy metabolism.

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na+/K+-ATPase and Ca2+-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.

Effect of Lead Exposure on Spontaneous Abortion: a Case-Control Study.

BACKGROUND: The aim of the study is to determine the effects of blood lead levels (BLLs) on spontaneous abortion. METHODS: A well-matched case-control study was performed at Peking Union Medical College Hospital from 2016 - 2018. Spontaneous abortion cases requiring suction and curettage within 12 weeks gestational age composed the case group. Control group includes pregnancies showing fetal cardiac activity with simultaneous requests for induced abortions matched to case group in age, gravidity, parity, and gestational age. RESULTS: Three hundred patients with 150 per group were included. Age, gravidity, parity, gestational age and the number of lead exposures, smokers, alcoholic beverage drinkers, and coffee drinkers were not significantly different between the two groups. The mean BLLs were 27.17 µg/L and 17.28 µg/L for the case and control group, respectively (p = 0.000). The odds ratios for spontaneous abortion comparing 5 - 9, 10 - 14, 15 - 24, 25 - 39, and ≥ 40 µg/L with a reference category of < 5 µg/L blood lead were 1.58 (0.23 - 10.90), 3.13 (2.11 - 9.08), 4.63 (1.45 - 14.83), 6.33 (1.95 - 20.56), and 22.56 (4.91 - 103.66), respectively, demonstrating a significant trend (P1 = 0.64, P2 = 0.02, P3 = 0.01, P4 = 0.02, and P5 = 0.00). CONCLUSIONS: Lead contamination and its effect on spontaneous abortion cannot be ignored. During early pregnancy, when BLL is above 10 µg/L, the chance of spontaneous abortion increases compared to BLLs below 5 µg/L. The higher the BLL is, the greater the risk of spontaneous abortion will be.

Assessment of the necessity of uterine artery embolization during suction and curettage for caesarean scar pregnancy: a prospective cohort study.

BACKGROUND: Uterine artery embolization (UAE) followed by suction and curettage is a common conservative treatment for caesarean scar pregnancy (CSP), but the advantages of suction and curettage alone are underestimated due to the lack of standards for selecting appropriate cases for which this approach would be applicable. We sought to identify indicators with which to assess the need for UAE during suction and curettage. METHODS: The prospective cohort consisted of 105 women diagnosed with CSP in Peking Union Medical College Hospital between January 2016 and September 2018 who were followed up until 60 days after surgery. The main outcome was the therapy used, and secondary outcomes included recovery, bleeding, surgery time, length of hospital stay, and total cost. RESULTS: We found that ß-human chorionic gonadotropin (ß-hCG) levels were significantly lower (P < 0.05), foetal cardiac activity was significantly lower (P < 0.05), the myometrial layer was significantly thicker (P < 0.05), expenditures were lower and lengths of hospital stay were shorter in patients who received suction and curettage alone (the non-UAE group) than in those who received UAE followed by suction and curettage (the UAE+ group). In addition, for CSP patients, UAE might be less necessary when the myometrial thickness is ≥2 mm and the gestational sacmeasures ≤5 cm, and suction and curettage alone may be safer for these patients. CONCLUSION: Suction and curettage alone is a more suitable option than UAE followed by suction and curettage because the former carries a lower cost, shorter length of hospital stay, and lower risk of adverse events. Regarding risk factors, patients with a lower uterine segment thickness ≥ 2 mm and a gestational mass diameter ≤ 5 cm have an increased probability of being successfully treated with suction and curettage alone.

Biomarkers of metal toxicity in embryos in the general population.

BACKGROUND: With the development of industrialization, public exposure to toxic metals could occur everywhere, eventually affecting individuals' reproductive systems and even embryos and leading to early pregnancy loss. The aim of the study was to determine the profile of toxic metal levels in pregnant women in the general population and to identify biomarkers for metal toxicity in embryos. METHODS: A case-control study with pregnant women was conducted at Peking Union Medical College Hospital in 2016-2018. Women who experienced spontaneous abortion within 12 weeks of gestation comprised the case group, and women with pregnancies showing fetal cardiac activity who requested an induced abortion almost simultaneously were included in the control group. Blood and urine specimen were tested for concentrations of cadmium, chromium, selenium, arsenic, and mercury. RESULTS: A total of 195 patients were enrolled, with 95 in the case group and 100 in the control group. Significant differences in gravidity, parity, history of miscarriage, mean blood cadmium levels, and mean urine chromium levels were present between the two groups (P1 = 0.013, P2 = 0.000, P3 = 0.000, P4 = 0.002, P5 = 0.046); the odds ratios in the spontaneous abortion with blood cadmium >0.4 µg/L, urine chromium >2 µg/L, gravity <3, parity <2, and history of miscarriage >1 compared with the induced abortion group were 1.26 (1.09, 1.85), 1.56 (1.23, 2.53), 1.39 (1.17, 1.98), 1.72 (1.21, 4.62), and 1.18 (1.06, 1.65), with P-values of 0.003, 0.031, 0.003, 0.247, and 0.001, respectively. CONCLUSION: Blood cadmium and urine chromium levels are two possible biomarkers of toxic metal embryotoxicity in the general population, which means that in the general population, blood cadmium >0.4 µg/L or urine chromium >2 µg/L might indicate an increased risk of spontaneous abortion.

Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery.

Microfluidic systems can accelerate clinical translation of nanoparticles due to their ability to generate nanoparticles in a well-controlled and reproducible manner. In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF. Tf-LNPs-MF was shown to have a smaller size and more uniform structures compared to LNPs produced by multi-steps BM method (Tf-LNPs-BM). Furthermore, efficient cellular uptake of Tf-LNPs-MF in vitro as well as greater tumor inhibition in vivo proved that Tf-LNPs-MF had higher siRNA delivery efficiency in vitro and in vivo. Taken together, this single-step microfluidic synthesis significantly simplified the Tf-LNPs production and improved their drug delivery properties and may serve as a valuable tool for developing new cancer therapies.

Investigation on the immunomodulatory activities of Sarcodon imbricatus extracts in a cyclophosphamide (CTX)-induced immunosuppressanted mouse model.

Aims: Sarcodon imbricatus, an edible fungus, is widely used in Asian medicine because of its significant pharmacological activities. In the present study, we investigated the immunomodulatory effects of polysaccharide-enriched S. imbricatus extracts (SP) in cyclophosphamide (CTX)-induced immunosuppressed mice. Results: Astragalus polysaccharide (AP) was used as a positive control. Compared with CTX-induced immunosuppressed mice, thirty-day SP treatment strongly enhanced the organ indexes of spleen and thymus and suppressed hind paw swelling. Both AP and SP increased the serum levels of immunoglobulin (IgA, IgG, and IgM), and suppressed the overproduction of interleukin-2 (IL-2). Moreover, SP reduced methane dicarboxylic aldehyde levels, and increased the total antioxidant capacity, superoxide dismutase, and glutathione peroxidase in both serum and liver tissues of CTX-induced immunosuppressed mice. Conclusion: S. imbricatus extracts significantly improved immune function in CTX-induced immunosuppressed mice via modulation of oxidative systems.

Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway.

Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2 and SMMC-7721 cells, CSEI reduced cell viability, enhanced apoptosis rate, caused reactive oxygen species (ROS) accumulation, inhibited migration ability, and induced caspases cascade and mitochondrial membrane potential dissipation. CSEI significantly inhibited HepG2-xenografted tumor growth in nude mice. In cell and animal experiments, CSEI increased the activations of pro-apoptotic proteins including caspase 8, caspase 9 and caspase 3; meanwhile, it suppressed the expressions of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and anti-oxidation proteins, such as nuclear factor-erythroid 2 related factor 2 (Nrf2) and catalase (CAT). The enhanced phosphorylation of P38 and c-JunN-terminalkinase (JNK), and decreased phosphorylation of extra cellular signal-regulated protein kinase (ERKs) were observed in CSEI-treated cells and tumor tissues. CSEI-induced cell viability reduction was significantly attenuated by N-Acetyl-l-cysteine (a ROS inhibitor) pretreatment. All data demonstrated that the upregulated oxidative stress status and the altered mitogen-activated protein kinases (MAPKs) phosphorylation contributed to CSEI-driven mitochondrial dysfunction. Taken together, CSEI exactly induced apoptosis in human hepatocellular carcinoma cells via ROS/MAPKs dependent mitochondrial pathway.

Aeration and fermentation strategies on nisin production.

OBJECTIVES: To optimize nisin production in Lactococcus lactis by using different aeration and fermentation strategies. RESULTS: The nisin titer and specific nisin production rate reached maximum values of 11,900 IU/ml and 4110 IU/g/h, respectively, in aerobic batch fermentation with glucose as C source. These values were higher than in anaerobic batch fermentation (10,700 IU/ml and 3260 IU/g/h, respectively). The maximum specific nisin production rates appeared earlier in aerobic batch fermentation, which suggests that nisin production is stimulated by aeration. Different fermentation strategies were compared: maximum nisin production (15,400 IU/ml) was achieved with fed-batch fermentation with a variable rate of feeding under aerobic conditions. CONCLUSION: Nisin production can be stimulated by aeration, which goes against the typical conditions involving strict anaerobiosis.

Enzymo-chemical preparation, physico-chemical characterization and hypolipidemic activity of granular corn bran dietary fibre.

Corn bran dietary fibre (CF) was paid more attention for its anticancer and hypolipidemic activities. In this paper, corn bran was firstly decomposed to the threadlike fibre (CF1) by multiple enzymes and then further modified to the granular fibre (CF2) by alkali under high pressure and high temperature (APT). The two types of fibres were characterized by scanning electron microscope (SEM) and near-infrared spectrophotometer (IR), and investigated by hydration measurements and nitrite adsorption assays. The results showed that CF2 had more much specific surface area, and displayed 4.7, 6.3 and 30-fold increases in water retention (WR), swelling capacity (SC) and nitrite absorption (NA), compared with CF1, respectively. The rat feeding trials showed that the granular fibre could decrease total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDLC) by 41.4 %, 20.7 % and 56.5 %, respectively. These excellent physiological activities indicate that CF2 will be a potentially available dietary ingredient in functional food industries, and meanwile imply that the enzymochemical method is a desired strategy for CF processing.

Quantitative proteomics analysis for effect of Acanthopanax senticosus extract on neuroinflammation.

Acanthopanax senticosus, a traditional herb commonly found in Northeastern Asia,has been used for treating neurodegenerative diseases. However, the molecular and cellular mechanisms of its effect on neuroinflammation have not been investigated. In the current study, quantitative proteomics approach was applied to investigate the effect of Acanthopanax senticosus extract (ASE) on nitrosative stress and inflammatory response in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). The results showed ASEinhibited LPS-induced nitric oxide (NO) production, while no significant toxicity appeared in the cells. Proteomic quantitative analyses using 2D-DIGE (Difference in Gel Electrophoresis) combined with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) revealed that 17 proteins showed significant changes responding to ASE. Furthermore, signal transduction pathways and network modulated by the ASE were predicted using Ingenuity Pathway Analysis (IPA). These findings indicated the ability of ASE to suppress LPS-induced nitrosative stress in BV-2 cells, and may provide important insights into the molecular mechanism underlying potentially beneficial effect of Acanthopanax senticosus.

Optimization of enzyme complexes for efficient hydrolysis of corn stover to produce glucose.

Hydrolysis of cellulose to glucose is the critical step for transferring the lignocellulose to the industrial chemicals. For improving the conversion rate of cellulose of corn stover to glucose, the cocktail of celllulase with other auxiliary enzymes and chemicals was studied in this work. Single factor tests and Response Surface Methodology (RSM) were applied to optimize the enzyme mixture, targeting maximum glucose release from corn stover. The increasing rate of glucan-to-glucose conversion got the higher levels while the cellulase was added 1.7µl tween-80/g cellulose, 300µg ß-glucosidase/g cellulose, 400µg pectinase/g cellulose and 0.75mg/ml sodium thiosulphate separately in single factor tests. To improve the glucan conversion, the ß-glucosidase, pectinase and sodium thiosulphate were selected for next step optimization with RSM. It is showed that the maximum increasing yield was 45.8% at 377µg/g cellulose Novozyme 188, 171µg/g cellulose pectinase and 1mg/ml sodium thiosulphate.

Deformable liposomes by reverse-phase evaporation method for an enhanced skin delivery of (+)-catechin.

BACKGROUND: (+)-catechin, as the most common catechin isomer, is recognized to be an antioxidant which benefits the skin in many ways. The purpose of the present study was to prepare and evaluate a suitable liposomal delivery systems for (+)-catechin topical application. METHODS: In this study, catechin-loaded conventional liposomal delivery system, deformable conventional liposomal delivery system and deformable liposomes prepared by reverse-phase evaporation (REV) method were compared. The three systems were characterized for liposome particle size, zeta-potential, entrapment efficiency, drug release, permeability across porcine skin and catechin deposition in the skin. RESULTS: It was revealed that the size of deformable conventional liposomes before freeze-drying and deformable REV liposomes after freeze-drying range from 335.6 ± 71.7 nm to 551.1 ± 53.4 nm, respectively, which were considered to be suitable for skin delivery. The deformable REV liposomes had a higher aqueous volume and thus were able to entrap greater amounts of hydrophilic (+)-catechin (50.0 ± 5.9%) compared to conventional (30.0 ± 3.8%) and deformable conventional liposomes (36.1 ± 4.6%). All liposomal formulations exhibited a prolonged catechin release. Compared to deformable liposomes, the REV deformable liposomes showed a significantly better deposition of (+)-catechin while catechin solution did not permeate into the porcine ear skin. CONCLUSION: Among all formulations studied, deformable REV liposomes were considered to be favorable for catechin topical delivery.

[Study on the detection of active ingredient contents of Paecilomyces hepiali mycelium via near infrared spectroscopy].

Partial least squares (PLS) and radial basis function neural network (RBFNN) combined with near infrared spectros- copy (NIR) were applied to develop models for cordycepic acid, polysaccharide and adenosine analysis in Paecilomyces hepialid fermentation mycelium. The developed models possess well generalization and predictive ability which can be applied for crude drugs and related productions determination. During the experiment, 214 Paecilomyces hepialid mycelium samples were obtained via chemical mutagenesis combined with submerged fermentation. The contents of cordycepic acid, polysaccharide and adenosine were determined via traditional methods and the near infrared spectroscopy data were collected. The outliers were removed and the numbers of calibration set were confirmed via Monte Carlo partial least square (MCPLS) method. Based on the values of degree of approach (Da), both moving window partial least squares (MWPLS) and moving window radial basis function neural network (MWRBFNN) were applied to optimize characteristic wavelength variables, optimum preprocessing methods and other important variables in the models. After comparison, the RBFNN, RBFNN and PLS models were developed successfully for cordycepic acid, polysaccharide and adenosine detection, and the correlation between reference values and predictive values in both calibration set (R2c) and validation set (R2p) of optimum models was 0.9417 and 0.9663, 0.9803 and 0.9850, and 0.9761 and 0.9728, respectively. All the data suggest that these models possess well fitness and predictive ability.

Screening for potential -α -Glucosidase inhibitors in Coptis chinensis franch extract using ultrafiltration LC-ESI-MSn.

Naturally existing -α -glucosidase inhibitors from traditional herbal medicines have attracted considerable interest to treat type 2 diabetes mellitus (T2DM). Hundreds of herbs have been reported to have the potential to inhibit -α -glucosidase. However, most common methods to examine the inhibitors of -α -glucosidase are usually time-consuming. In the current study, the screening of -α -glucosidase ligands from Coptis chinensis Franch extract was undertaken by ultrafiltration liquid chromatography coupled to electrospray ionization tandem mass spectrometry (ultrafiltration LC-ESI-MS(n)). Resultantly, the enzyme inhibition studies showed that Coptis chinensis Franch extract carries the strongest -α -glucosidase inhibitory activity among the five kinds of Chinese herbal extracts. Subsequently, five compounds that could bind to -α -glucosidase in the Coptis chinensis Franch extract were found using ultrafiltration liquid chromatography, and their structures were identified by ESI-MS(n) to be coptisine, epiberberine, jatrorrhizine, berberine, palmatine. Cumulatively, these results were anticipated to be encouraging for applying the Coptis chinensis Franch extracts as efficient anti-diabetic drug candidates.

Structure characterisation of polysaccharides purified from Boletus aereus Bull. and its improvement on AD-like behaviours via reliving neuroinflammation in APP/PS1 mice.

The water-soluble neutral polysaccharide BEP2, with a molecular weight of 26.65 kDa, was isolated from the aqueous extract obtained from the fruiting bodies of Boletus aereus Bull. BEP2 primarily comprises Gal, with specific site substitutions speculated at partial positions, such as the substitution of -OCH3 at position H-3 or the branch at position C-2 including α-L-Fucp-(1→, α-D-Manp-(1 â†’ and α-D-Manp-(1 â†’ 3)-α-L-Fucp-(1 â†’ 6)-ß-D-Glcp-(1→. Treatment with BEP2 significantly enhanced learning, memory, and cognitive function, while concurrently reducing the accumulation of ß-amyloid and suppressing neuroinflammation within the brains of APP/PS1 mice. Based on the results of biochemical detection, gut microbiota analysis, and metabolomic profiling, we found that BEP2 significantly upregulated the abundance of two bacterial families while downregulation that of seven bacterial families within the intestinal ecosystem. Notably, the abundance of the S24-7 family was significantly increased. Treatment with BEP2 upregulated five metabolites, while downregulating three metabolites, including norepinephrine. Additionally, BEP2 decreased the levels of interleukin (IL)-1ß and IL-6, regulated the activities of microglial cells and astrocytes and increased the levels of the chemokine fractalkine (CX3CL1) and its receptor on microglia (CX3CR1), as well as that of transforming growth factor (TGF)-ß1. These findings confirmed the suppressive effects of BEP2 on neuroinflammation.

Long-acting formulation of a new muscarinic receptor antagonist for the treatment of overactive bladder.

A new muscarinic receptor antagonist, 5-hydroxymethyl tolterodine (5-HMT), was successfully encapsulated into PLGA microspheres. With an increase of PLGA concentration from 15% to 40%, encapsulation efficiency of 5-HMT increased from 55.39% to 76.32%, and the particle size of microsphere increased from 34.33 to 70.48 µm. Increasing the homogenisation speed from 850 to 2300 rpm, the particle size was reduced about 65%.The in vitro and in vivo studies in beagle dogs show that the release profile of 5-HMT-loaded microspheres (5-HMT MS) prepared with 503H is characterised by a low initial burst followed by slow release that lasted for 2 weeks. A C(max) of 1.617 ± 0.392 ng/mL was found on the sixth day. When evaluated for inhibition of the carbachol-induced contraction of rat urinary bladder, 5-HMT MS showed a much longer and more potent effect than tolterodine tablets. The mean urination time of the rats in the 5-HMT MS group was significantly decreased (p < 0.05 or p < 0.01) to less than 2 weeks.

Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer.

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.