Co-assembled Supramolecular Hydrogel of Salvianolic Acid B and a Phosphopeptide for Enhanced Wound Healing.

Supramolecular natural product gels (NPGs) have emerged as promising biomaterials for scalable and adjustable drug delivery systems. These gels possess biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Salvianolic acid B (SAB), derived from Salvia miltiorrhiza, a Chinese medicinal plant, exhibits various beneficial properties such as antioxidant, antifibrotic, and angiogenic effects. In our research, we serendipitously discovered that the co-assembly of SAB and a soluble phosphopeptide results in the formation of a robust and adhesive hydrogel termed 1&SAB hydrogel. This hydrogel effectively prolongs the retention time of the therapeutic agents on the skin's wound surface, thereby promoting wound healing. The hydrogel demonstrates antioxidant effects, enhances cell migration, accelerates angiogenesis, and inhibits scar hyperplasia. This innovative gel material offers a simple and efficient approach to managing skin wounds and holds promise for application in complex wound-healing treatments.

Structural Characteristics of Polysaccharide GP2a in Gardenia jasminoides and Its Immunomodulatory Effect on Macrophages.

Here, we elucidated the structural characteristics of a polysaccharide isolated from Gardenia jasminoides Ellis (labeled as GP2a) and its immunomodulatory activity. GP2a is an acidic polysaccharide with a molecular weight of 44.8 kDa, mostly comprising galacturonic acid. Methylation analysis revealed 4-GalpA (74.8%) to be the major sugar residue in GP2a. Nuclear magnetic resonance analysis indicated that its main chain comprised →4)-α-D-GalpA-6-OMe-(1→4)-α-D-GalpA-(1→ and →4)-α-D-GalpA-6-OMe-(1→2)-α-L-Rhap-(1→, with galactan and arabinans linked to the C-4 position of →2)-α-L-Rhap-(1→ residue as branched chains. Furthermore, GP2a showed no obvious toxicity to macrophages (RAW 264.7) while enhancing cell viability in a dose- and time-dependent manner. Compared with untreated cells, nitric oxide production and secretion of cytokines, such as tumor necrosis factor-α, interferon-γ, interleukin (IL)-1ß, IL-6, and granulocyte macrophage colony stimulating factor, in GP2a-treated cells significantly increased after 48 h. At 300 µg/mL GP2a concentration, there was no significant difference in the cytokine levels in GP2a- and lipopolysaccharide-treated cells (the positive control). In summary, GP2a is a pectic polysaccharide with homogalacturonan and rhamnogalacturonan-I structural regions in the main chain. Based on its immunomodulatory effects in vitro, GP2a may have potential uses in functional food and medicine.

Antiviral Therapy with Entecavir following Antituberculosis Therapy Alleviates Liver Injury and Restores Innate Immunity in Tuberculosis Patients Coinfected with Hepatitis B Virus.

OBJECTIVE: Coinfection of tuberculosis (TB) and viral hepatitis may increase the risk of antituberculosis treatment-induced hepatotoxicity, which is regarded as a common cause of termination of the first-line antituberculosis drugs. The study aimed at investigating the protective effects of antiviral therapy on the liver and innate immunity in patients with TB-HBV coinfection. METHODS: A total of 100 patients with TB-HBV coinfection were recruited and split into antituberculosis and antiviral groups, 50 per group, according to odd or even date of hospital admission from December 2019 to October 2020. The patients in the anti-TB group received antituberculosis therapy, and those in the antiviral group received antiviral therapy. The clinical effectiveness; HBV-DNA negative conversion rate; liver function assessment involving alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL); immune function evaluation including CD4+, CD8+, CD4+/CD8+, and CD3+ T cells; inflammatory cytokines containing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ); and intestinal microflora including bifidobacterium, lactobacillus, enterobacterium, enterococcus, and clostridium were main outcome measures after treatment. RESULTS: It was found that the total response rate in the antiviral group was significantly higher than the anti-TB group after treatment (χ 2 = 3.157, P=0.017). There was a significant difference in HBV-DNA negative conversion rates between the antiviral group and anti-TB group (82% vs. 58%, χ 2 = 6.384, P=0.001). The ALT, AST, and TBIL in the two groups were all increased after treatment (P < 0.05), but the antiviral group indicated a rise of the above indices compared to the anti-TB group (P < 0.05). The two groups showed a rise on the concentration of CD3+, CD4+, and CD4+/CD8+ T cells and a decline on the CD8+ T cells after treatment (P < 0.05), but these changes in the antiviral group were more evident to those in the anti-TB group (P < 0.05). There was an increase on the IFN-γ level and decrease on the TNF-α and IL-6 levels in both groups after treatment (P < 0.05), but the antiviral group revealed a higher level of IFN-γ with lower levels of TNF-α and IL-6 compared to the anti-TB group (P < 0.05). After treatment, the number of bifidobacteria and lactobacilli was increased, and the number of enterobacteria, enterococci, and clostridium were decreased in the two groups (P < 0.05), while these changes in the antiviral group were more remarkable compared to the anti-TB group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ2 = 0.267, P=0.731). CONCLUSION: Antiviral therapy for tuberculosis-HBV coinfected patients could inhibit HBV replication, providing protection against liver damage, improving innate immunity, and balancing intestinal microflora.

Semen Brassicae reduces thoracic aortic remodeling, inflammation, and oxidative damage in spontaneously hypertensive rats.

BACKGROUND: This study aimed to evaluate the role of Semen Brassicae, a common Traditional Chinese Medicine, in the treatment of hypertension. METHODS: Spontaneously hypertensive rats (SHRs) were divided into five groups and were gavaged with either distilled water, water-decocted solution from Semen Brassicae (0.5, 1 or 2 g/kg), or nifedipine (2.7 mg/kg). Normal rats gavaged with distilled water were used as a control. Systolic (SBP) and diastolic blood pressure (DBP) were measured using a non-invasive method. After 8 weeks of administration, all animals were anesthetized. Abdominal aortic serum was collected to measure serum factors; the thoracic aorta was collected for hematoxylin and eosin staining and western blot analysis. RESULTS: Both SBP and DBP were significantly decreased after Semen Brassicae treatment. Endothelin-1 and angiotensin II levels in abdominal aortic serum, as well as the levels of inflammatory factors interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha, were significantly decreased after Semen Brassicae treatment. The wall thickness of the thoracic aorta was significantly reduced after Semen Brassicae treatment. Nitric oxide level and the activity of superoxide dismutase and glutathione peroxidase were significantly increased, and malondialdehyde level was significantly decreased in the abdominal aortic serum after Semen Brassicae treatment. Semen Brassicae treatment increased the levels of peroxisome proliferator-activated receptor gamma and IκB-α and decreased the levels of intercellular adhesion molecule 1, monocyte chemoattractant protein-1, von Willebrand factor, p-IκB-α and p-p65 NF-κB. CONCLUSIONS: In conclusion, water-decocted solution from Semen Brassicae can decrease blood pressure, improve vascular remodeling, and attenuate oxidative stress and inflammation in SHRs.

Pretreatment of Root Canal with Photodynamic Therapy Facilitates Adhesion, Viability and Differentiation of Stem Cells of the Apical Papilla.

This study was to test the hypothesis that root canal pretreated with photodynamic therapy (PDT) would promote stem cells from the apical papilla (SCAP) adhesion, proliferation and differentiation without affecting smear layer removal and microhardness of root canal. Standardized root canals were randomized into four groups (n = 30/group): (1) sodium hypochlorite(NaOCl) group, (2) NaOCl + ethylene diaminetetraacetic acid (EDTA) group, (3) NaOCl + PDT group, (4) NaOCl + EDTA + PDT group. After treatments, smear layer removal and microhardness of root canal were evaluated. SCAP with hydroxyapatite-based scaffolds were seeded into root canals for 7 days. SCAP adhesion was observed by scanning electron microscope (SEM), and viable cells were calculated by CellTiter-Glo Luminescent kit. Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) expression of SCAP were evaluated by Quantitative Reverse Transcriptase-Polymerase Chain Reaction. There was no significant difference in the smear layer removal and microhardness of root dentin between the groups with and without PDT treatment (P > 0.05). SCAP with elongated cytoplasmic processes and cell-cell contact were observed on the dentin surfaces treated with PDT. Elevated cell viability, PDGF and VEGF expression were found in root canal treated with PDT (P < 0.05). Under the experimental conditions, PDT could provide positive microenvironment for SCAP growth.

[Quality evaluation of Styrax based on quantitative determination of 7 chemical components using HPLC wavelength switching method and chemometrics].

In order to evaluate the quality of Styrax more comprehensively,this study attempted to establish an HPLC wavelength switching method to simultaneously determine the content of seven compounds in Styrax,and chemometrics were used to analyze the quality difference between different sources of Styrax,and finally establish a characteristic chromatogram of Styrax. The column was Agilent ZORBAX Extend C18( 4. 6 mm×250 mm,5 µm) with phase a mixture of acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase in a gradient elution procedure; the detection wavelength was set as follows: 0-13. 5 min,194 nm( benzoic acid);13. 5-20. 5 min,278 nm( cinnamic acid); 20. 5-32 min,194 nm( benzyl benzoate,benzyl cinnamate,cinnamyl cinnamate,dehydroabietic acid); 32-55 min,241 nm( abietic acid). The methodological verification results showed that when the injection masses of benzoic acid,cinnamic acid,benzyl benzoate,benzyl cinnamate,cinnamyl cinnamate,dehydroabietic acid and abietic acid were0. 006 948-0. 694 8,0. 001 426-0. 142 6,0. 013 16-0. 658 0,0. 006 148-0. 614 8,0. 008 035-0. 803 5,0. 002 121-0. 212 1,and0. 010 172-1. 017 2 µg,respectively,there were good linear relationship between injection mass and peak area. The average recovery rates of seven compounds were in the range from 94. 34% to 105. 8%,and all RSD were less than 3. 0%( n = 6). The methodological verification results showed that the developed HPLC wavelength switching method has good accuracy and repeatability. The results of the sample analysis showed that the quality of Styrax from different sources was quite different. The chromatogram of Styrax reference material( S1) was used as the reference chromatogram to calculate the fingerprint similarity of each batch of samples. The results showed that the similarities of samples S2-S10 were 0. 952,0. 949,0. 981,0. 351,0. 751,0. 969,0. 979,0. 992 and 0. 971,respectively.The similarity values of other batches samples were satisfactory,except for sample S5 and S6,indicating that the quality difference among these samples is small. The similarity values of S11-S20 were 0. 060,0. 055,0. 054,0. 285,0. 092,0. 002,0. 044,0. 044,0. 044,and 0. 040,respectively. The results showed that compared with the sample S1,there was a large quality difference among S11-S20. Based on the chromatograms of S1-S10,the HPLC characteristic chromatograms of Styrax was established and the purpose is to give reference to other pharmaceutical researchers. The newly developed HPLC wavelength switching method have the advantages of simplicity,reproducibility and specificity,and the developed HPLC characteristic chromatograms provided a reference method for the overall quality evaluation of Styrax.

Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3.

Modified citrus pectin (MCP) is a carbohydrate enriched complex, which has been implicated in cancer treatment and prevention. However, the effects of MCP on urinary bladder cancer (UBC) are unknown. In this study, MCP was first tested in T24 and J82 human UBC cells and showed the inhibition of cell viability by the sulforhodamine B (SRB) assay. The MCP-treated UBC cells exhibited G2/M phase arrest with the decrease of Cyclin B1 and phosphorylated Cdc2. Caspase-3 was also activated, leading to the cleavage of Caspase-3 and PARP. We further explored the possible molecular mechanisms upon MCP treatment in UBC cells. Reduction of galectin-3 was observed and followed with the inactivation of Akt signaling pathway. Of note, galectin-3 knockdown by RNA interference recapitulated the MCP-mediated anti-proliferation, cell cycle arrest and apoptosis. Moreover, oral administration of MCP to the T24 xenograft-bearing nude mice inhibited the tumor growth significantly (P < 0.05). Quantification analysis of immunohistochemistry staining for Ki67 and cleaved Caspase-3 confirmed the decrease of proliferation index (P < 0.05) and the increase of apoptosis index (P < 0.01) in 700 mg/kg MCP-fed UBC xenografts. Using the information from TCGA database, we revealed that the overexpression of galectin-3 was associated with high tumor grade with lymph node metastasis, poor overall survival in UBC patients. Considering the remarkable inhibitory effects of MCP on UBC cell proliferation and survival in vitro and in vivo mainly through galectin-3, which is upregulated in UBCs, MCP may become an attractive agent, as a natural dietary fiber, for prevention and therapy of UBCs.

Optimized QuEChERS Method Combined with UHPLC-MS/MS for the Simultaneous Determination of 15 Mycotoxins in Liquorice.

In our study, a reliable and rapid analytical method for the simultaneous determination of 15 mycotoxins (aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, alternariol, agroclavine, citrinin, diacetoxyscirpenol, deoxynivalenol, fumonisin B1, fumonisin B2, ochratoxin A, sterigmatocystin, T-2 toxin, and zearalenone) in liquorice using ultra-HPLC coupled to tandem MS was developed and validated. Due to the complex ingredients in liquorice, we chose a QuEChERS-based extraction procedure as the sample pretreatment. Meanwhile, for the first time, acetate buffer was used to replaced water, which can greatly reduce the concentration of formic acid in acetonitrile, which further reduces the extraction efficiency of impurities. The optimal combination of adsorbents is 150 mg primary secondary amine, 150 mg silica gel, 600 mg octadecylsilane, and 900 mg anhydrous magnesium sulfate. Electrospray ionization in both positive- and negative-ionization modes was applied to detect all the mycotoxins in a single run time of 15 min, with LOQs in the range of 0.125-2.5 µg/kg. The recoveries of determination obtained were in the range of 81.0-104.7%, whereas the analytes could be accurately quantified in the 0.25-625 µg/kg concentration range, with all coefficients being >0.992. Intra- and interday reproducibility were lower than 5.5 and 8.9%, respectively, for all analytical mycotoxins. The validated method was finally applied to screen mycotoxins in 31 batches of real samples collected from drugstores and hospitals in Shanghai, China. Our survey findings show that six mycotoxins were detected, including alternariol, citrinin, deoxynivalenol, fumonisin B1, ochratoxin, and zearalenone, and that the positive rate of mycotoxins was 54.8% in real samples, ranging from 3.37 to 520.6 µg/kg.

T2 relaxation time for intervertebral disc degeneration in patients with upper back pain: initial results on the clinical use of 3.0 Tesla MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is a useful non-invasive tool for evaluating abnormalities of intervertebral discs. However, there are few studies which applied functional MRI techniques to investigate degenerative changes in cervical and cervicothoracic junction (CTJ) spine among adults. The aim of this study was to compare T2 relaxation time measurement evaluation with morphological grading for assessing cervical and CTJ intervertebral discs (IVD) in the patients suffering neck, shoulder, and upper back pain. METHODS: Sixty-three patients (378 IVDs) and 60 asymptomatic volunteers (360 IVDs) of the cervical and CTJ discs were assessed using a 3.0 T magnetic resonance imaging (MRI) protocol, including an sagittal T2 relaxation time protocol. The relaxation time values of the nucleus pulposus (NP) were recorded and all discs were visually graded according to Pfirrman's grading system. The correlation between T2 relaxation time values and qualitative clinical grading of degeneration, patient age, sex and anatomic level were analyzed RESULTS: There is a clear trend of decreasing mean T2 values of the NP associate with increasing Pfirrmann grades (C2-T1) for both patients and asymptotic volunteers. Significant T2 differences were seen among grades I-V (P < 0.05). However, grade V was not observed in the CTJ. Linear correlation analysis revealed a strong negative association between T2 values of the NP and Pfirrmann grade (r = -0.588, r = -0.808) of C2-7 and C7T1. Age were also significantly correlated NP T2 values (r = -0.525, r = -0.723) for patients and volunteers. Moreover, the receiver operating characteristic analysis for average measures in a range from 0.70-0.79 (C2-7) to 0.84-0.89 (C7T1) for patients. CONCLUSIONS: T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of IVD degeneration and age-associated disc changes.

The radiation protection role of heparin-SOD conjugate in irradiated mice

ABSTRACT Heparin-SOD conjugate (Hep-SOD) was prepared by modifying Cu,Zn-SOD with heparin. An acute radiation-induced mouse injury model was constructed to study the radiation protection effects of Hep-SOD conjugate. Fifty-six mice were randomly divided into seven groups: (I) normal control group; (II) irradiated control group; (III) positive control group (amifostine group, 300 mg/kg); (IV) SOD group (35000 U/kg); (V) high dosage of Hep-SOD group (70000 U/kg); (VI) medium dosage of Hep-SOD group (35000 U/kg); (VII) low dosage of Hep-SOD group (17500 U/kg). Drugs were intraperitoneally injected into each mouse 1 h before radiation except for the normal control group. All the irradiated groups were irradiated with 6 Gy. Organ indices, haematopoietic function indices, peripheral blood cells, liver function test, oxidative stress state and pathological observation were detected to study the effects of Hep-SOD on irradiated mice. Results showed that bone marrow suppression of irradiated mice could be reduced when treated by Hep-SOD before radiation. Oxidative stress detection and pathological observation of the liver and intestine showed that the damage caused by radiation was relieved when mice were treated with Hep-SOD before radiation. This study shows a new direction to prevent organisms from the damage caused by radiation.

Effectiveness of Sonic, Ultrasonic, and Photon-Induced Photoacoustic Streaming Activation of NaOCl on Filling Material Removal Following Retreatment in Oval Canal Anatomy.

OBJECTIVE: This study aimed to assess the effectiveness of sonic, ultrasonic and laser [photon-induced photoacoustic streaming (PIPS)] irrigation activation in removing filling remnants from oval root canals after standard canal retreatment procedures with the ProTaper universal rotary retreatment system. METHODS: Twenty-eight maxillary first premolars were instrumented with ProTaper NiTi rotary instruments and obturated with gutta-percha and AH Plus sealer using the continuous wave of condensation technique. After storage at 37°C and 100% humidity for 1 week, the specimens were retreated with the ProTaper universal retreatment system for the removal of filling material. Teeth were then randomly assigned into four groups (n = 7): group 1, positive control; group 2, retreated with sonic irrigation; group 3, retreated with ultrasonic irrigation; and group 4, retreated with laser irradiation. The specimens were scanned using micro-CT before instrumentation, after obturation and mechanical retreatment, and after additional activation procedures. The percentage volume of the filling remnants was measured. Specimens were split longitudinally after micro-CT scan, canal walls were examined using scanning electron microscopy (SEM), and the amount of residual filling material was scored. RESULTS: The filling materials' removal efficacy in the three experimental groups was higher than that of the control group (p < 0.05), whereas filling materials ranging from 1.46 ± 0.30 to 2.21 ± 0.46 mm(3) remained in the canal in all three experimental groups. Additionally, there was a significantly greater reduction in the amount of filling remnants in the PIPS group than in the sonic and ultrasonic groups (both p < 0.05), and significantly greater reduction in the ultrasonic group than the sonic group (p < 0.05). CONCLUSIONS: Activation of NaOCl with PIPS showed significantly better performance than sonic and ultrasonic techniques in removing the filling remnants following mechanical retreatment of oval root canals. The ultrasonic technique also performed better than the sonic technique. However, none of the additional activation procedures was able to completely eliminate the filling remnants.

Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia.

Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar), we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg) were administered to the Dazhui (DU14), Qihai (RN6) and Mingmen (DU4) of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14), Qihai (RN6) and Mingmen (DU4). Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

[Preliminary study on general regulations for processing of different processing procedures of prepared slices of Chinese crude drugs in China].

General regulations for the processing are the important part of processing procedures of prepared slices of Chinese crude drugs. It has an important significance on enhancing the operability of actual production, regulating production of prepared slices of Chinese crude drugs, improving quality and establishing drug safety. The article could provides suggestions and reference for future compilation work on "National processing procedures of prepared slices of Chinese crude drugs" by comparative analysis and summary on general regulations for the processing of different processing procedures of prepared slices of Chinese crude drugs in China.

Quantitative capillary electrophoresis and its application in analysis of alkaloids in tea, coffee, coca cola, and theophylline tablets.

A quantitative CE (qCE) system with high precision has been developed, in which a 4-port nano-valve was isolated from the electric field and served as sample injector. The accurate amount of sample was introduced into the CE system with high reproducibility. Based on this system, consecutive injections and separations were performed without voltage interruption. Reproducibilities in terms of RSD lower than 0.8% for retention time and 1.7% for peak area were achieved. The effectiveness of the system was demonstrated by the quantitative analysis of caffeine, theobromine, and theophylline in real samples, such as tea leaf, roasted coffee, coca cola, and theophylline tablets.

Preparation and evaluation of C18-bonded 1-microm silica particles for pressurized capillary electrochromatography.

Nonporous silica spheres (1 microm) were synthesized and bonded with octadecylsilane functionality. These stationary phase particles were packed electrokinetically into fused-silica capillaries with 100 microm id for a length of 20 cm, which was evaluated by using pressurized CEC (pCEC). The efficiency of the C18 RP column was characterized through the theoretical plates of thiourea, benzyl alcohol, toluene, styrene, and naphthalene. The effects of experimental parameters such as the applied voltage, sample size, pump flow rate, pH value and the concentration of the buffer solution, and the content of methanol in the mobile phase, on-column efficiency were evaluated. Column efficiency as high as 200 000 theoretical plates per meter for naphthalene was obtained with the optimal condition of 70% v/v methanol and 30% v/v of 10 mmol/L phosphate buffer (pH 7.8) at an applied voltage of 10 kV and a supplementary pressure of 500 psi.