A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Development and external validation of a quantitative diagnostic model for malignant gastric lesions in clinical opportunistic screening: A multicenter real-world study.

BACKGROUND: Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. METHODS: We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. RESULTS: This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750-0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570-0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. CONCLUSION: This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Targeted arginine metabolomics combined with metagenomics revealed the potential mechanism of Pueraria lobata extract in treating myocardial infarction.

The extraction methods for traditional Chinese medicine (TCM) may have varying therapeutic effects on diseases. Currently, Pueraria lobata (PL) is mostly extracted with ethanol, but decoction, as a TCM extraction method, is not widely adopted. In this study, we present a strategy that integrates targeted metabolomics, 16 s rDNA sequencing technology and metagenomics for exploring the potential mechanism of the water extract of PL (PLE) in treating myocardial infarction (MI). Using advanced analytical techniques like ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we comprehensively characterized PLE's chemical composition. Further, we tested its efficacy in a rat model of MI induced by ligation of the left anterior descending branch of the coronary artery (LAD). We assessed cardiac enzyme levels and conducted echocardiograms. UPLC-MS/MS was used to compare amino acid differences in serum. Furthermore, we investigated fecal samples using 16S rDNA sequencing and metagenomic sequencing to study intestinal flora diversity and function. This study demonstrated PLE's effectiveness in reducing cardiac injury in LAD-ligated rats. Amino acid metabolomics revealed significant improvements in serum levels of arginine, citrulline, proline, ornithine, creatine, creatinine, and sarcosine in MI rats, which are key compounds in the arginine metabolism pathway. Enzyme-linked immunosorbent assay (ELISA) results showed that PLE significantly improved arginase (Arg), nitric oxide synthase (NOS), and creatine kinase (CK) contents in the liver tissue of MI rats. 16 s rDNA and metagenome sequencing revealed that PLE significantly improved intestinal flora imbalance in MI rats, particularly in taxa such as Tuzzerella, Desulfovibrio, Fournierella, Oscillibater, Harryflintia, and Holdemania. PLE also improved the arginine metabolic pathway in the intestinal microorganisms of MI rats. The findings indicate that PLE effectively modulates MI-induced arginine levels and restores intestinal flora balance. This study, the first to explore the mechanism of action of PLE in MI treatment considering amino acid metabolism and intestinal flora, expands our understanding of the potential of PL in MI treatment. It offers fresh insights into the mechanisms of PL, guiding further research and development of PL-based medicines.

Preparation, Characterization, and Anti-Lung Cancer Activity of Tetrandrine-Loaded Stealth Liposomes.

Background: Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, is a potential candidate for cancer chemotherapy. However, Tet has poor aqueous solubility and a short half-life, which limits its bioavailability and efficacy. Liposomes have been widely utilized to enhance the bioavailability and efficacy of drugs. Methods: In this study, Tet-loaded stealth liposomes (S-LPs@Tet) were prepared by ethanol injection method. Furthermore, physicochemical characterisation, biopharmaceutical behaviour, therapeutic efficacy, and biocompatibility of S-LPs@Tet were assessed. Results: The prepared S-LPs@Tet had an average particle size of 65.57 ± 1.60 nm, a surface charge of -0.61 ± 0.10 mV, and an encapsulation efficiency of 87.20% ± 1.30%. The S-LPs@Tet released Tet in a sustained manner, and the results demonstrated that the formulation remained stable for one month. More importantly, S-LPs significantly enhanced the inhibitory ability of Tet on the proliferation and migration of lung cancer cells, and enabled Tet to escape phagocytosis by immune cells. Furthermore, in vivo studies confirmed the potential for long-circulation and potent tumor-suppressive effects of S-LPs@Tet. Moreover, ex vivo and in vivo safety experiments demonstrated that the carrier material S-LPs exhibited superior biocompatibility. Conclusion: Our research suggested that S-LPs@Tet has potential applications in lung cancer treatment.

Dengzhanshengmai capsule alleviates heart failure and concomitantly decreases phenylacetylglutamine level, interacting with the intestinal microflora in rats.

Heart failure (HF) is an advanced stage of most heart diseases. Some studies reported that Dengzhanshengmai (DZSM) capsule may improve HF, but its mechanisms are unclear. This study attempts to determine the function of DZSM in treating HF and investigates its potential mechanism. We demonstrated that DZSM can considerably reduce systemic inflammation, improve intestinal barrier functions and enhance cardiac functions in HF rats. Further investigations displayed that the beneficial effects of DZSM were related to the reduction of gut microbiota metabolite phenylacetylglutamine (PAGln) levels in serum and heart tissue. In addition, we demonstrated that PAGln can exacerbate the severity of HF in rats, and the serum PAGln levels in HF patients were higher than in healthy subjects. Moreover, by using microbial sequencing, we found that DZSM could alter the composition and function of the intestinal microbiota in HF rats, including decreased relative abundance of Turicibacter and Turicibacter_sp.TS3, and regulated the gene expression of PAGln synthesis-related enzymes. Therefore, our findings have contributed novel perspectives on the involvement of DZSM in treating HF, specifically in its regulation of intestinal flora and associated detrimental metabolites. Furthermore, our results have offered empirical evidence supporting the utilization of DZSM as a therapeutic approach for HF.

Cell-derived biomimetic nanoparticles for the targeted therapy of ALI/ARDS.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common clinical critical diseases with high morbidity and mortality. Especially since the COVID-19 outbreak, the mortality rates of critically ill patients with ARDS can be as high as 60%. Therefore, this problem has become a matter of concern to respiratory critical care. To date, the main clinical measures for ALI/ARDS are mechanical ventilation and drug therapy. Although ventilation treatment reduces mortality, it increases the risk of hyperxemia, and drug treatment lacks safe and effective delivery methods. Therefore, novel therapeutic strategies for ALI/ARDS are urgently needed. Developments in nanotechnology have allowed the construction of a safe, efficient, precise, and controllable drug delivery system. However, problems still encounter in the treatment of ALI/ARDS, such as the toxicity, poor targeting ability, and immunogenicity of nanomaterials. Cell-derived biomimetic nanodelivery drug systems have the advantages of low toxicity, long circulation, high targeting, and high bioavailability and show great therapeutic promises for ALI/ARDS owing to their acquired cellular biological features and some functions. This paper reviews ALI/ARDS treatments based on cell membrane biomimetic technology and extracellular vesicle biomimetic technology, aiming to achieve a significant breakthrough in ALI/ARDS treatments.

Immunity-and-matrix-regulatory cells enhance cartilage regeneration for meniscus injuries: a phase I dose-escalation trial.

Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Ethanol extract of Pueraria lobata improve acute myocardial infarction in rats via regulating gut microbiota and bile acid metabolism.

BACKGROUND AND AIM: Acute myocardial infarction (AMI) is a multifactorial disease with high mortality rate worldwide. Ethanol extract of Pueraria lobata (EEPL) has been widely used in treating cardiovascular diseases in China. This study aimed to explore the underlying therapeutic mechanism of EEPL in AMI rats. EXPERIMENTAL PROCEDURE: We first evaluated the anti-AMI efficacy of EEPL through immunohistochemistry staining and biochemical indexes. Then, UPLC-MS/MS, 16S rDNA, and shotgun metagenomic sequencing were used to analyze the alterations in bile acid metabolism and intestinal flora. Finally, the influence of EEPL on ilem bile acid metabolism, related enzymes expression, and transporter proteins expression in rats were verified by mass spectrometry image and ELISA. KEY RESULTS: The results showed that EEPL can reduce cardiac impairment in AMI rats. Besides, EEPL effectively increased bile acid levels and regulated gut microbiota disturbance in AMI rats via increasing CYP7A1 expression and restoring intestinal microbiota diversity, separately. Moreover, it can increase bile acids reabsorption and fecal excretion through inhibiting FXR-FGF15 signaling pathway and increasing OST-α expression, which associated with Lachnoclostridium. CONCLUSIONS AND IMPLICATIONS: Our findings demonstrated that EEPL alleviated AMI partially by remediating intestinal dysbiosis and promoting bile acid biosynthesis, which provided new targets for AMI treatment.

Precise nanodrug delivery systems with cell-specific targeting for ALI/ARDS treatment.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and critical diseases in clinics and have no effective treatment to date. With the concept of "precision medicine", research into the precise drug delivery of therapeutic and diagnostic drugs has become a frontier in nanomedicine research and has entered the era of design of precise nanodrug delivery systems (NDDSs) with cell-specific targeting. Owing to the distinctive characteristics of ALI/ARDS, designing NDDSs for specific focal sites is an important strategy for changing drug distribution in the body and specifically increasing drug concentration at target sites while decreasing drug concentration at non-target sites. This strategy enhances drug efficacy, reduces adverse reactions, and ensures accurate nano-targeted treatment. On the basis of the characteristics of pathological ALI/ARDS microenvironments, this paper reviews NDDSs targeting vascular endothelial cells, neutrophils, alveolar macrophages, and alveolar epithelial cells to provide reference for designing accurate NDDSs for ALI/ARDS and novel insights into targeted treatments for ALI/ARDS.

Spatially resolved metabolomics combined with bioactivity analyses to evaluate the pharmacological properties of two Radix Puerariae species.

ETHNOPHARMACOLOGICAL RELEVANCE: P. lobata and P. thomsonii are medicinal plants with similar pharmacological functions but different therapeutic effects. A novel method is presented herein to investigate metabolites in terms of their distribution and qualification, quantification is necessary to elucidate the different therapeutic effects of the two Puerariae species. AIM OF THE STUDY: The aim of the present study was to perform spatially resolved metabolomics combined with bioactivity analyses to systematically compare the metabolite differences in P. lobata and P. thomsonii by distribution, qualification, quantification, and biological activity to evaluate their pharmacological properties. MATERIALS AND METHODS: Air flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was performed to characterize the differences in the metabolite distributions of P. lobata and P. thomsonii. Further qualitative and quantitative analyses of the differential metabolites were performed using liquid chromatography-mass spectrometry (LC-MS). Biological activities correlated with the differences in the metabolites were validated by MTT assays. RESULTS: Some metabolites showed complementary distributions of the phloem and xylem in the two species, saccharide, vitamin, and inosine levels were higher in the phloem of P. thomsonii but higher in the xylem of P. lobata. The 3'-hydroxyl puerarin level was higher in the xylem of P. thomsonii but higher in the phloem of P. lobata. Qualitative and quantitative analyses of the metabolites revealed a total of 52 key differential metabolites. MTT assays showed that daidzein, daidzin, puerarin, ononin, genistin, formononetin, 3'-hydroxy puerarin, 3'-methoxy puerarin, mirificin, and 3'-methoxy daidzin exerted protective effects on H9c2 cells against hypoxia/reoxygenation injury. P. lobata extracts exhibited a significantly better protective efficacy than P. thomsonii extracts. CONCLUSIONS: In this study, AFADESI-MSI combined with LC-MS and biological activities comprehensively elucidated metabolite differences in the distribution, qualification, quantification, and pharmacological properties of P. lobata and P. thomsonii. The results of this study could provide a novel strategy for species identification and quality assessment of similar Chinese herbal medicines.

Discovery of a novel, liver-targeted thyroid hormone receptor-ß agonist, CS271011, in the treatment of lipid metabolism disorders.

Introduction: Thyroid hormone receptor ß (THR-ß) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-ß agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. Methods: We conducted luciferase reporter gene assays to assess the activation of THR-ß and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. Results: Compared with MGL-3196, CS271011 showed higher THR-ß activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. Conclusions: CS271011 is a potent and liver-targeted THR-ß agonist for treating lipid metabolism disorders.

Development and External Validation of an Improved Version of the Diagnostic Model for Opportunistic Screening of Malignant Esophageal Lesions.

We aimed to develop an improved version of the diagnostic model predicting the risk of malignant esophageal lesions in opportunistic screening and validate it in external populations. The development set involved 10,595 outpatients receiving endoscopy from a hospital in Hua County, a high-risk region for esophageal squamous cell carcinoma in northern China. Validation set A enrolled 9453 outpatients receiving endoscopy in a non-high-risk region in southern China. Validation set B involved 17,511 residents in Hua County. The improved diagnostic model consisted of seven predictors including age, gender, family history of esophageal squamous cell carcinoma, smoking, body mass index, dysphagia, and retrosternal pain, with an area under the receiver operating characteristic curve (AUC) of 0.860 (95% confidence interval: 0.835-0.886) in the development set. Ideal discrimination ability was achieved in external validations (AUC validation set A: 0.892, 95% confidence interval: 0.858-0.926; AUC validation set B: 0.799, 95% confidence interval: 0.705-0.894). This improved model also markedly increased the detection rate of malignant esophageal lesions compared with universal screening, demonstrating great potential for use in opportunistic screening of malignant esophageal lesions in heterogeneous populations.

Improving Reporter Gene Assay Methodology for Evaluating the Ability of Compounds to Restore P53 Activity.

Tumor suppressor protein P53 induces cycle arrest and apoptosis by mediating the transcriptional expression of its target genes. Mutations causing conformational abnormalities and post-translational modifications that promote degradation are the main reasons for the loss of P53 function in tumor cells. Reporter gene assays that can scientifically reflect the biological function can help discover the mechanism and therapeutic strategies that restore P53 function. In the reporter gene system of this work, tetracycline-inducible expression of wild-type P53 was used to provide a fully activated state as a 100% activity reference for the objective measurement of biological function. It was confirmed by RT-qPCR, cell viability assay, immunofluorescence, and Western blot analysis that the above-mentioned reporter gene system could correctly reflect the differences in biological activity between the wild-type and mutants. After that, the system was tentatively used for related mechanism research and compound activity evaluation. Through the tetracycline-induced co-expression of wild-type P53 and mutant P53 in exact proportion, it was observed that the response modes of typical transcriptional response elements (TREs) to dominant negative P53 mutation effect were not exactly the same. Compared to the relative multiple-to-solvent control, the activity percentage relative to the 100% activity reference of wild-type P53 can better reflect the actual influence of the so-called P53 mutant reactivator. Similarly, relative to the 100% activity reference, it can objectively reflect the biological effects caused by the inhibitor of P53 negative factors, such as MDM2. In conclusion, this study provides a 100% activity reference and a reliable calculation model for relevant basic research and drug development.

Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications.

The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.

CS12192, a Novel JAK3/JAK1/TBK1 Inhibitor, Synergistically Enhances the Anti-Inflammation Effect of Methotrexate in a Rat Model of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common disease worldwide and is treated commonly with methotrexate (MTX). CS12192 is a novel JAK3 inhibitor discovered by Chipscreen Biosciences for the treatment of autoimmune diseases. In the present study, we examined the therapeutic effect of CS12192 against RA and explored if the combinational therapy of CS12192 and MTX produced a synergistic effect against RA in rat collagen-induced arthritis (CIA). Arthritis was induced in male Sprague-Dawley rats by two intradermal injections of bovine type II collagen (CII) and treated with MTX, CS12192, or the combination of CS12192 and MTX daily for two weeks. Effects of different treatments on arthritis score, X-ray score, pathology, and expression of inflammatory cytokines and biomarkers were examined. We found that treatment with either CS12192 or MTX produced a comparable therapeutic effect on CIA including: (1) significantly lowering the arthritis score, X-ray score, serum levels of rheumatic factor (RF), C-reactive protein (CRP), and anti-nuclear antibodies (ANA); (2) largely alleviating histopathological damage, reducing infiltration of Th17 cells while promoting Treg cells; (3) inhibiting the expression of inflammatory cytokines and chemokines such as IL-1ß, TNF-α, IL-6, CCL2, and CXCL1. All these inhibitory effects were further improved by the combinational therapy with MTX and CS12192. Of importance, the combinational treatment also resulted in a marked switching of the Th17 to Treg and the M1 to M2 immune responses in synovial tissues of CIA. Thus, when compared to the monotherapy, the combination treatment with CS12192 and MTX produces a better therapeutic effect against CIA with a greater suppressive effect on T cells and macrophage-mediated joint inflammation.

Aurantiamide Acetate Ameliorates Lung Inflammation in Lipopolysaccharide-Induced Acute Lung Injury in Mice.

Purpose: Aurantiamide acetate (AA) is a dipeptide derivative with complex pharmacological activities and remarkable effects on preventing and treating various diseases. In the current study, we aimed to investigate whether AA can exert protective effects in a mouse model of ALI induced by LPS. Materials and Methods: In this model, mice were given intranasal LPS for 3 days prior to receiving AA (2.5, 5, and 10 mg/kg) via oral gavage. An assessment of histopathological changes was performed by hematoxylin and eosin (HE). Proinflammatory cytokines were detected in bronchoalveolar lavage fluids (BALFs) by enzyme-linked immunosorbent assays (ELISAs). The effects of AA on protein expression of NF-κB and PI3K/AKT signaling pathways were determined by Western blot. In addition, lung wet/dry (W/D) weight ratio, myeloperoxidase (MPO) activity, cell counts, and protein content were also measured. Results: According to results, AA pretreatment significantly reduced lung pathological changes, W/D ratio, MPO activity, and protein content. Additionally, AA resulted in a significant reduction in the number of total cells, neutrophils, and proinflammatory cytokines in the BALF after LPS stimulation. The subsequent study revealed that pretreatment with AA dose dependently suppressed LPS-induced activation of NF-κB as well as PI3K/AKT phosphorylation. Conclusion: The results indicated that the AA had a protective effect on LPS-induced ALI in mice and could be a potential drug for ALI.

Recent trends in platelet membrane-cloaked nanoparticles for application of inflammatory diseases.

Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.

An Evolving Role of Aqueous Piperazine to Improve the Solubility of Non-Steroidal Anti-Inflammatory Drugs.

Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs-PIP salts, such as ibuprofen-piperazine (IBU-0.5PIP) salt, indomethacin-piperazine (IND-0.5PIP) salt, sulindac-piperazine (SUL-0.5PIP) salt, phenylbutazone-piperazine (PBZ-0.5PIP) salt, ketoprofen-piperazine (KPF-0.5PIP) salt and flurbiprofen-piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.

Spinal dI4 Interneuron Differentiation From Human Pluripotent Stem Cells.

Spinal interneurons (INs) form intricate local networks in the spinal cord and regulate not only the ascending and descending nerve transduction but also the central pattern generator function. They are therefore potential therapeutic targets in spinal cord injury and diseases. In this study, we devised a reproducible protocol to differentiate human pluripotent stem cells (hPSCs) from enriched spinal dI4 inhibitory GABAergic INs. The protocol is designed based on developmental principles and optimized by using small molecules to maximize its reproducibility. The protocol comprises induction of neuroepithelia, patterning of neuroepithelia to dorsal spinal progenitors, expansion of the progenitors in suspension, and finally differentiation into mature neurons. In particular, we employed both morphogen activators and inhibitors to restrict or "squeeze" the progenitor fate during the stage of neural patterning. We use retinoic acid (RA) which ventralizes cells up to the mid-dorsal region, with cyclopamine (CYC), an SHH inhibitor, to antagonize the ventralization effect of RA, yielding highly enriched dI4 progenitors (90% Ptf1a+, 90.7% Ascl1+). The ability to generate enriched spinal dI4 GABAergicINs will likely facilitate the study of human spinal IN development and regenerative therapies for traumatic injuries and diseases of the spinal cord.

Preparation, characterization, and anti-colon cancer activity of oridonin-loaded long-circulating liposomes.

In this study, oridonin-loaded long-circulating liposomes (LC-lipo@ORI) were prepared with the ethanol injection method. Its physicochemical properties and the morphology were characterized, and its stability and release profiles were evaluated. Furthermore, its antitumor effects were studied using two in vitro cell models of colon cancer and two tumor-bearing models in nude mice. The prepared LC-lipo@ORI was quasi-spherical, with a mean particle size of 109.55 ± 2.30 nm. The zeta potential was -1.38 ± 0.21 mV, the encapsulation efficiency was 85.79%±3.25%, and the drug loading was 5.87%±0.21%. In vitro release results showed that the cumulative release rate of LC-lipo@ORI at 12 h was 63.83%. However, ORI dispersion was almost completely released after 12 h. In vitro cytotoxicity results showed that, the inhibiting effects of LC-lipo@ORI on the proliferation of two types of colon cancer cells were apparently higher than those of ORI dispersion, whereas those of the blank carrier were not noticeable. In vivo studies confirmed that, the encapsulation of LC-lipo enhanced the inhibitory effects of ORI on tumor growth. These results indicated that LC-lipo@ORI a promising formulations for colon cancer treatment.