Fabrication of mesoporous silica nanoparticles for releasable delivery of licorice polysaccharide at the acne site in topical application.

Glycyrrhizae Radix et rhizome/licorice is a precious herb in traditional Chinese medicine (TCM). TCM's polysaccharides are medicinally active. But herbal polysaccharides pose some limitations for topical applications. Therefore, this study aimed to utilize licorice polysaccharide via mesoporous silica nanoparticles (MSN) for anti-acne efficacy in topical delivery. The polysaccharide (GGP) was extracted with a 10 % NaOH solution. Chemical characterization suggested that GGP possesses an Mw of 267.9 kDa, comprised primarily of Glc (54.1 %) and Ara (19.12 %), and probably 1,4-linked Glc as a backbone. Then, MSN and amino-functionalized MSN were synthesized, GGP entrapped, and coated with polydopamine (PDA) to produce nanoparticle cargo. The resulted product exhibited 76 % entrapment efficiency and an in vitro release of 89 % at pH 5, which is usually an acne-prone skin's pH. Moreover, it significantly increased Sebocytes' cellular uptake. GGP effectively acted as an anti-acne agent and preserved its efficacy in synthesized nanoparticles. In vivo, the results showed that a 20 % gel of MSN-NH2-GGP@PDA could mediate an inflammatory response via inhibiting pro-inflammatory cytokines and regulating anti-inflammatory cytokines. The MSN-NH2-GGP@PDA inhibited TLR2-activated-MAPK and NF-κB pathway triggered by heat-killed P. acnes. In conclusion, fabricated MSN entrapped GGP for biomimetic anti-acne efficacy in topical application.

Pharmacokinetics, tissue distribution, and subacute toxicity of oral carrageenan in mice.

Carrageenan (CGN) is a typical sulfated polysaccharide widely applied in the food and pharmaceutical industries. Its in vivo behavior plays vital roles in understanding structural and biological functional relationships. The lack of UV chromophores in highly sulfated polysaccharides presents a challenge for their in vivo behavior studies. Therefore, this study aimed to develop a fast and effective quantitative fluorescence method for investigating the pharmacokinetics and tissue distribution of CGN. Fluorescence isothiocyanate labeling of CGN (FCGN) and microplate reader-based measurements were developed and validated to study its pharmacokinetics. These results showed that the FCGN concentration peaked at 3 h, the mean residence time was 36.6 h, and the clearance rate was 0.1 L/h/kg. Most of the FCGN was excreted in the feces, while 9.2 % was excreted in the urine, suggesting absorption and metabolism. The pharmacokinetic parameters indicated that the FCGN was absorbed quickly, eliminated slowly, and could remain in the body for a sustained profile. Moreover, ex vivo imaging and quantification of FCGN in tissues revealed that FCGN accumulated in the liver and kidney. Furthermore, oral administration of CGN or KOs for 14 days led to changes in liver and kidney indices. Histological analysis of significant organs revealed hepatocyte necrosis in the liver, renal tubular vacuolization in the kidney, and incomplete colonic epithelial cells. The KOs had a more significant effect on inflammatory cell infiltration than did CGNs. These in vivo findings laid the foundation for the study and application of CGN in food and pharmaceutical applications.

An active derivatization detection method for inline monitoring the isolation of carbohydrates by preparative liquid chromatography.

Polysaccharides have unique physio-chemical properties and various biological functions and have rapidly expanded interest over the last two decades. The purification of polysaccharides and their degraded oligosaccharides is challenging because carbohydrates have no chromophore and need a proper detector to monitor the chromatographic elution process. This study proposed an active derivatization detection (ADD) method based on active splitting from post-column flow, a microchannel reactor for efficient derivatization of polysaccharide reducing sugars with p-hydroxybenzoic acid hydrazide, and in-line detection by the UV detector of liquid chromatography system. The method and device were validated by the use of 11 monosaccharides, sulfated oligosaccharides (from degraded carrageenan), and polysaccharides (from Zizania latifolia). It has shown much better performance than the traditional phenol-sulfuric acid method (gold standard). Moreover, the ADD module presumes an add-in to the original preparative LC system, independent of the scale of the purification process and type of system. The developed method is versatile for chromatographic separation of carbohydrates and lays the foundation for their subsequent studies.

Dynamic expression analysis of peripheral blood derived small extracellular vesicle miRNAs in sepsis progression.

Immune disorders caused by sepsis have recently drawn much attention. We sought to dynamically monitor the expression of small extracellular vesicle (sEV) miRNAs in peripheral blood during sepsis to explore these miRNAs as potential biomarkers for monitoring immune function in sepsis patients. This study included patients with sepsis. Blood samples were obtained from 10 patients on the first through 10th days, the 12th day and the 14th day since sepsis onset, resulting in 120 collected samples. Serum sEVs were extracted from peripheral venous blood, and levels of MIR497HG, miR-195, miR-497, and PD-L1 in serum sEVs were detected by qPCR, and clinical information was recorded. Our study revealed that the levels of MIR497HG, miR-195, miR-497 and PD-L1 in serum sEVs showed periodic changes; the time from peak to trough was approximately 4-5 days. The levels of sEV MIR497HG and miR-195 had a positive linear relationship with SOFA score (r values were -0.181 and -0.189; p values were 0.048 and 0.039, respectively). The recorded quantities of sEV MIR497HG, miR-195 and PD-L1 showed a substantial correlation with ARDS. ROC curve analysis revealed that sEV MIR497HG, miR-195 and miR-497 could predict the 28-day mortality of sepsis patients with an AUC of 0.66, 0.68 and 0.72, respectively. Levels of sEVs MIR497HG, miR-195, miR-497 and PD-L1 showed periodic changes with the immune status of sepsis, which provides a new exploration direction for immune function biomarkers and immunotherapy timing in sepsis patients.

Extraction, structure, pharmacological activities and applications of polysaccharides and proteins isolated from snail mucus.

Snail mucus had medical applications for wound healing as early as ancient Greece and the late Han Dynasty (China). A literature search found 165 modern research papers discussing the extraction methods, chemical compositions, pharmacological activities, and applications of snail mucus. Thus, this review summarized the research progress on the extraction, structure, pharmacological activities, and applications of polysaccharides and proteins isolated from snail mucus. The extraction methods of snail mucus include natural secretion and stimulation with blunt force, spray, electricity, un-shelling, ultrasonic-assisted, and ozone-assisted. As a natural product, snail mucus mainly comprises two polysaccharides (glycosaminoglycan, dextran), seven glycoproteins (mucin, lectin), various antibacterial peptides, allantoin, glycolic acid, etc. It has pharmacological activities that encourage cell migration and proliferation, and promote angiogenesis and have antibacterial, anti-oxidative and anticancer properties. The mechanism of snail mucus' chemicals performing antibacterial and wound-healing was proposed. Snail mucus is a promising bioactive product with multiple medical applications and has great potential in the pharmaceutical and healthcare industries. Therefore, this review provides a valuable reference for researching and developing snail mucus.

Temperature management in the intensive care unit: a practical survey from China.

Introduction: Temperature management is an important aspect of the treatment of critically ill patients, but there are differences in the measurement and management of temperature in different Intensive Care Units (ICUs). The objective of this study was to understand the current situation of temperature measurement and management in ICUs in China, and to provide a basis for standardized temperature management in ICUs.Methods: A 20-question survey was used to gather information on temperature management strategies from ICUs across China. Data such as method and frequency of temperature measurement, management goals, cooling measures, and temperature management recommendations were collected.Results: A total of 425 questionnaires from unique ICUs were included in the study, with responses collected from all provinces and autonomous regions in China. Mercury thermometers were the most widely used measurement tool (82.39%) and the axilla was the most common measurement site (96.47%). There was considerable variability in the frequency of temperature measurement, the temperature at which intervention should begin, intervention duration, and temperature management goals. While there was no clearly preferred drug-based cooling method, the most widely used equipment-based cooling method was the ice blanket machine (93.18%). The most frequent recommendations for promoting temperature management were continuous monitoring and targeted management.Conclusion: Our investigation revealed a high level of variability in the methods of temperature measurement and management among ICUs in China. Since fever is a common clinical symptom in critically ill patients and can lead to prolonged ICU stays, we propose that standardized guidelines are urgently needed for the management of body temperature (BT) in these patients.

Efficacy and Safety of Remimazolam Tosilate Combined With Esketamine for Analgesic Sedation in Mechanically Ventilated ICU Patients: A Single-Arm Clinical Study Protocol.

Introduction: Patients in the intensive care unit (ICU) frequently experience increased heart rate, blood pressure, and respiration rate as a product of anxiety and restlessness about their condition and treatments. Analgesia and sedation commonly involve benzodiazepines or opioids that lead to respiratory suppression and other adverse reactions. Remimazolam tosilate is a short-acting GABAA receptor agonist with reduced cardiovascular and respiratory inhibition compared to other commonly used benzodiazepines. Esketamine is a non-competitive N-methyl-D-aspartic acid (NMDA) receptor inhibitor that inhibits hyperalgesia and prolongs postoperative analgesia. It also reduces postoperative pain, delirium, and the use and acute tolerance of opioids. This study aims to assess the efficacy and safety of remimazolam tosilate combined with esketamine and sufentanil for sedation and analgesia in mechanically ventilated ICU patients. Methods and Analysis: This prospective, single-arm, single-center, open-label clinical trial will be conducted from January 2022 to December 2023. The study will include 200 adult patients (≥ 18 years) from Shandong Provincial Hospital (affiliated with Shandong First Medical University) who are mechanically ventilated and admitted to the ICU between 24 and 72 h from the time of ventilation and who are administered analgesia and sedatives. Patients will undergo arterial blood gas analysis before administration. Remimazolam tosilate (0.2 mg/kg) will be injected intravenously within 30 s, followed by continuous infusion at a rate of 0.1 to 0.3 mg/kg/h via micropump. Esketamine (0.25 mg/kg) will be injected intravenously and maintained at 0.15 mg/kg/h, while sufentanil will be maintained at the rate of 0.1 to 0.2 µg/kg/h. The primary study outcome is the overall time required to maintain sedation. Secondary outcomes will include the total dosage used to reach the target sedation level, total mechanical ventilation time, awakening time, length of hospital stay, and incidence of cardiorespiratory-related adverse events and delirium. Adverse events (AEs) will be reported regardless of their relationship to the experimental drugs. AEs associated with adverse drug reactions will be classified as "affirmative correlation," "possible relevance," and "unable to determine." A paired t-test or Wilcoxon signed-rank test will be used to compare the changes of observed indexes before and after treatment. A P < 0.05 will be considered statistically significant. Ethics and Dissemination: This study was approved by the local ethics committee at Shandong Provincial Hospital affiliatied to Shandong First Medical University. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial Registration: The trial is registered at the Chinese Clinical Trial Registry: ChiCTR2100053106; date of registration: 2021-11-10.