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Wound healing is a slow and complex biological process, including inflammatory reaction, cell proliferation, cell differentiation, cell migration, angiogenesis, extracellular matrix deposition, tissue remodeling, and so on. Wnt signaling pathway can be divided into classical pathway and non-classical pathway. Wnt classical pathway, also known as Wnt/β-catenin signaling pathway, plays an important role in cell differentiation, cell migration, and maintenance of tissue homeostasis. Many inflammatory factors and growth factors are involved in the upstream regulation of this pathway. The activation of Wnt/β-catenin signaling pathway plays an important role in the occurrence, development, regeneration, repair and related treatment of skin wounds. This article review the relationship between Wnt/β-catenin signaling pathway and wound healing, meanwhile summarizes its effects on important processes of wound healing, such as inflammation, cell proliferation, angiogenesis, hair follicle regeneration, and skin fibrosis, as well as the role of inhibitors of Wnt signaling pathway in wound healing.
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Humans , Wnt Signaling Pathway , Cell Differentiation , Cell Movement , Cell Proliferation , Inflammation , Wound HealingABSTRACT
With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.
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Rats , Animals , Drugs, Chinese Herbal/pharmacology , Rats, Sprague-Dawley , Serotonin , Metabolomics , WaterABSTRACT
The combination of Shuanghuanglian injection (SHLI) and ciprofloxacin injection (CIPI) is frequently prescribed in clinical practice, but the basis for the combination is weak. In this study, isothermal titration calorimetry and ultraviolet-visible absorption spectrometry were applied to identify the molecular interactions of SHLI and its main components, chlorogenic acid and neochlorogenic acid with CIPI. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and cold-spray ionization mass spectrometry were performed to confirm that this molecular interaction was related to the formation of self-assembled supramolecular systems induced by chlorogenic acid and neochlorogenic acid with CIPI through weak intermolecular bonds. The antibacterial activity toward Pseudomonas aeruginosa (P. aeruginosa) was evaluated via molecular interactions, and the inhibitory ability of SHLI, chlorogenic acid and neochlorogenic acid against P. aeruginosa was significantly reduced after interaction with CIPI. A molecular docking study demonstrated that the reduced antibacterial ability was closely related to the competitive binding of drug molecules to the same binding site of the DNA gyrase B (GyrB) subunit of P. aeruginosa. The present study uncovered the intermolecular interactions of SHLI and its main components chlorogenic acid and neochlorogenic acid with CIPI from the perspective of molecular self-assembly and contribute to the reduction of its antibacterial ability, providing a basis for the clinical combination of SHLI and CIPI.
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The joint application of traditional Chinese medicine injection containing chlorogenic acid (CA) and cefotaxime sodium (CS) is sometimes appeared in clinical practice, but the scientific basis of drug molecular compatibility is still weak. This study proposes a sequential analysis strategy based on isothermal titration calorimetry (ITC), cold-spray ionization mass spectrometry (CSI-MS) and antibacterial activity test to evaluate the molecular interactions between CA and CS. The results of ITC experiments showed that the Gibbs free energy ΔG < 0 and it was driven by enthalpy change when CA titrated CS, suggesting CA could spontaneously chemically react with CS. Subsequently, the parent ions (m/z 808.143 5) of binding molecular of CA and CS was detected by CSI-MS, indicating CA could chemically bond with CS. Furtherly, the antibacterial experiments found the antibacterial ability of CS against Klebsiella pneumonia was significantly reduced (P < 0.01) by CA in mixed solution. Finally, molecular docking technology showed CA and CS have a common target of penicillin binding protein 3 (PBP3), suggesting that the phenomenon of CA reduced the antibacterial ability of CS may be related to the competitive binding of two components with PBP3. Our studies have shown that CA could spontaneously chemically bond to CS and reduced its antibacterial ability, providing scientific data for molecular interaction evaluation of CA and CS.
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Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.
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Artificial Intelligence , Drug Combinations , Machine Learning , TechnologyABSTRACT
Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.
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Humans , Anti-Bacterial Agents/therapeutic use , Fractures, Bone/diagnostic imaging , Osteomyelitis/therapyABSTRACT
We review the representatives literatures on chronic osteomyelitis, sum up the new insights in recent years into diagnostic options and treatment regimens, analyze the advantages and disadvantages of various diagnostic approaches and treatment strategies, and propose areas of interest to make current diagnostic and treatment strategies more specific.
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Objectives:This study aims to analyze the current status of the collaboration of medical staff among county,township,and village with comprehensive prevention and control of chronic diseases based on nine dimen-sions of DMIC integrated medical service development model,with a view to providing medical services collaboration on chronic diseases across the organization to provide direction for improvement. Methods:278 health workers sam-pled by the combination of typical sampling and multi-stage random sampling method received a questionnaire and the results were analyzed statistically. Results:According to the findings of this study,village doctors show higher partic-ipation in chronic care collaboration,but they are faced with the aging population and most of them are poorly educat-ed;the multi-institutional collaboration is of low efficiency in practice although it is well accepted by all health work-ers;there is no existing shared health information system among county,township and village. Conclusion:These re-sults suggest that the government should strengthen its leadership and promote primary health care management through medical staff collaboration;initiatives of health workers should be stimulated to promote the continuity of medical serv-ices;the shared health information system should be set up to facilitate the health workers' collaboration.
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BACKGROUND: It is an urgent problem to effectively make bone marrow mesenchymal stem cells exert proper effects under hypoxic preconditioning. OBJECTIVE: To investigate the effects of diazoxide, a Mito-KATPchannel activator, on the proliferation and apoptosis of mouse BMSCs in hypoxic environment. METHODS: Mouse BMSCs were divided into four groups: blank control group, 0.16, 0.8, 4 μmol/L diazoxide groups. Cells intervened by diazoxide were cultured in a 10% O2incubator. MTT assay was performed to detect cell proliferation at 1, 2, 4, 6, 8 days after intervention, and Hoechst 33258 staining was performed to observe cell apoptosis at 14 days after intervention. RESULTS AND CONCLUSION: High homogeneity and purity but low proliferation of BMSCs was found. There was no significant difference in the activity of BMSCs among 0.16, 0.8, 4 μmol/L diazoxide groups (P > 0.05). In the blank control group, concentrated nuclei were dark blue in color and aggregated, and several round apoptotic bodies were found. In the diazoxide groups, apoptotic bodies were occasionally found, and no significant difference was found among different diazoxide groups. These findings indicate that a certain concentration of diazoxide can reduce cell apoptosis but has no effects on the proliferation of mouse BMSCs under hypoxic environment (10% O2).
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BACKGROUND:β-tricalcium phosphate (β-TCP) and monocalciumphosphate monohydrate (MCPM) are traditionally considered as reactants for dicalcium phosphate dehydrate (DCPD) bone cement,but little is reported on the hydroxyapatite (HA) as a reactant.OBJECTIVE:To verify whether HA and MCPM can be used to prepare DCPD bone cement and to explore the physicochemical properties.METHODS:The HA and β-TCP were prepared by wet chemical precipitation method,and mixed with appropriate proportion of MCPM.Then,the HA-DCPD and β-TCP-DCPD were obtained by adding a proper amount of curing water.The composition and structure of the two materials were analyzed by X-ray diffraction,the morphology was observed by scanning electron microscope,and the mechanical strength was tested by Instron5567 universal material test machine.These two kinds of materials were placed in simulated body fluid for detecting the weight loss ratio,soaked for 14 days and taken out for X-ray diffraction and scanning electron microscope detection.RESULTS AND CONCLUSION:X-ray diffraction findings indicated that these two kinds of materials both belonged to high-purity DCPD bone cement.Under the scanning electron microscope,β-TCP-DCPD bone cement had dense crystal structure,with less pore number;however,the HA-DCPD bone cement presented with finer grains,loose structure,and higher pore number.With the increase of curing time,the mechanical strength of two kinds of bone cements was correspondingly increased,but the compressive strength of β-TCP-DCPD bone cement was significantly higher than that of HA-DCPD bone cement (P ＜ 0.05).In the simulated body fluid,the weight loss ratio of β-TCP-DCPD bone cement was significantly lower than that of HA-DCPD bone cement (P ＜ 0.05).At 14 days after soaking in the simulated body fluid,a layer of spherical particles that was formed on the surface of both materials was identified as hydroxyapatite by scanning electron microscope observation and X-ray diffraction analysis.In summary,HA-DCPD bone cement has good biodegradability,excellent bioactivity and bone conductivity,but poor mechanical properties.
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To investigate the non-alkaloidal chemical constituents of the stems and leaves of Melodinus suaveolens and their antibacterial activities. Compounds were isolated and purified by repeated silica gel, Sephadex LH-20, RP18, and preparative HPLC. Their structures were elucidated by comparison with published spectroscopic data, as well as on the basis of extensive spectroscopic analysis. The antibacterial screening assays were performed by the dilution method. Fourteen compounds were isolated, and identified as lycopersene (1), betulinic aldehyde (2), 3β-acetoxy-22,23,24,25,26,27-hexanordammaran-20-one (3), 3a-acetyl-2, 3, 5-trimethyl-7a-hydroxy-5-(4,8,12-trimethyl-tridecanyl)-1,3a,5,6,7,7a-hexahydro-4-oxainden-1-one (4), 3β-hydroxy-28-norlup-20(29)-ene-17β-hydroperoxide (5), 3β-hydroxy-28-norlup-20(29)-ene-17α-hydroperoxide (6), β-sitosterol (7), 28-nor-urs-12-ene-3β, 17β-diol (8), α-amyrin (9), ergosta-4,6,8(14),22-tetraen-3-one (10), 3β-hydroxy-urs-11-en-28,13β-olide (11), betulin (12), obtusalin (13), and ursolic acid (14). Among the isolates, compounds 1, 2, 6, 8, 10, and 14 showed potent antibacterial activities against the four bacteria. This is the first report of the antibacterial activity of the constituents of Melodinus suaveolens.
Subject(s)
Anti-Bacterial Agents , Chemistry , Apocynaceae , Chemistry , Drugs, Chinese Herbal , Chemistry , Plant Leaves , Chemistry , Plant Stems , ChemistryABSTRACT
Objective: To study the chemical constituents from the stems and leaves of Cryptolepis buchananii. Methods: Compounds were isolated and purified by chromatography on silica gel, Sephadex LH-20, ODS columns, and preparative HPLC. Their structures were identified by NMR and MS, as well as comparison on spectral data with literature values. Results: Thirteen compounds were obtained from the EtOAc fraction of methanol extract in the stems and leaves of C. buchananii and their structures were elucidated as isoscopoletin (1), (+)-3-hydroxy-β-ionone (2), (3R, 6R, 7E)-3-hydroxy-4, 7-megastigmadien-9-one (3), ficusic acid (4), (+)-pinoresinol (5), (+)-8-hydroxypinoresinol (6), (+)-syringaresinol (7), diaaurantiamide acetate (8), loliolide (9), (-)-balanophonin (10), chrysoeriol (11), 9-hydroxy-10E, 12Z-octadecadienoic acid methyl ester (12), and ficusesquilignan A (13). Conclusion: All the compounds are isolated from the plants of Cryptolepis R. Br. for the first time.
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Objective:To evaluate the influence of hepatitis B virus (HBV) genome nucleotide A1846T mutation on the viral replication capacity and the transcription activity of HBV core promoter (CP) in vitro. Method A total of 385 patients with hepatitis B admitted to the 302 Hospital of PLA were enrolled in the study, including 116 with moderate chronic hepatitis B (CHB-M), 123 with severe chronic hepatitis B (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Serum HBV DNA was isolated and full-length HBV genome was amplified. The incidence of A1846T was analyzed. Full-length HBV genomes containing 1846T mutation were cloned into pGEM-T easy vector, and the counterpart wild-type 1846A plasmids were obtained by sitedirected mutagenesis. The full-length HBV genome was released from recombinant plasmid by BspQ /Sca digestion, and then transfected into HepG2 cells. Secreted HBsAg level and intracellular HBV core particles were measured 72 hours post-transfection to analyze the replication capacity (a 1.0-fold HBV genome model). 1846 mutant and wild-type full-length HBV genomes were extracted to amplify the fragment of HBV CP region, and the dual luciferase reporter of the pGL3-CP was constructed. The luciferase activity was detected 48 hours post-transfection. Result The incidence of A1846T mutation gradually increased with the severity of hepatitis B, reaching 31.03%, 42.27%, and 55.48% in CHB-M, CHB-S and ACLF patients respectively (P0.01). The replication capacity of 1846T mutants, level of secreted HBsAg, and transcriptional activity of CP promoter were increased by 320%, 28% and 85% respectively, compared with 1846A wild-type strains. While the more common double mutation A1762T/ G1764A in CP region was increased by 67%, 9% and 72% respectively, compared with its counterpart wild-type strains. A1846T had a greater influence on viral replication capacity in vitro. Conclusions A1846T mutation could significantly increase the replication capacity of hepatitis B virus, secretion of HBsAg and transcription activity of CP promoter, and cis-activate the downstream gene transcription. The finding indicates that HBV genome A1846T mutation might play a role in liver disease progression.
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<p><b>OBJECTIVE</b>To investigate the prevalence of benign prostatic hyperplasia (BPH) in Pingliang City of Gansu Province.</p><p><b>METHODS</b>We performed a cross-sectional randomized study of 836 men aged > or = 40 years from 26 communities of Pingliang, obtained their IPSS, measured the prostate volume by transabdominal ultrasonography, recorded the maximum flow (Qmax) by uroflowmetry, and processed the data by one-way analysis of variance.</p><p><b>RESULTS</b>Totally 820 subjects meeting the study criteria were included in the investigation. The men ranged in age from 40 to 83 years, averaging 61.5 years. The mean IPSS, prostate volume and Qmax were 9.3 +/- 7.8, (29.2 +/- 18.6) ml and (15.3 +/- 7.2) ml/s, respectively, all correlated with age. The prevalence of moderate-severe lower urinary tract symptoms (LUTS) was 46.8% (384/820). The prostate volume was > 20 ml in 63.5% (521/820), and Qmax <15 ml/s in 48.5% (398/805) of the subjects. The incidence rate of BPH, defined as IPSS >7, Qmax <15 ml/s and prostate volume > 20 ml, was 23.5% (193/820).</p><p><b>CONCLUSION</b>Among the men aged > or = 40 years in Pingliang, LUTS and prostate volume were correlated positively, while Qmax negatively with age, and the prevalence of BPH was 23.5%.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , China , Epidemiology , Organ Size , Prevalence , Prostate , Pathology , Prostatic Hyperplasia , Diagnosis , EpidemiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence of hyposexuality, erectile dysfunction (ED) and defective ejaculation (DE) in the old and middle-aged males in Pingliang area.</p><p><b>METHODS</b>This investigation included 1 539 men aged > or = 50 years from 6 urban districts and 20 villages in the suburbs of Pingliang City, Gansu Province. We recorded and analyzed their scores on IIEF-5 and Brief Male Sexual Function Inventory for Urology (O'Leary 1995).</p><p><b>RESULTS</b>A total of 1 230 subjects met the investigation criteria. They averaged 62.5 +/- 9.6 years of age (range 50-89 years), and were divided into four age groups: 50-59, 60-69, 70-79 and > or = 80 years. The mean scores on IIEF-5 were 0-25 (9.4 +/- 8.6), sexual desire 0-8 (2.3 +/- 2.1), and ejaculation 0-8 (3.6 +/- 3.0). Hyposexuality, ED and DE were defined as sexual desire score < or = 2, IIEF-5 score = 0-21, and ejaculation score < or = 2, respectively. Based on these criteria, the incidence rates of hyposexuality, ED and DE were 57.96%, 92.27% and 36.91%, respectively, with statistically significant differences among different age groups (P < 0.01).</p><p><b>CONCLUSION</b>The prevalence of ED, hyposexuality and DE, particularly the incidence of ED, is positively correlated with the increase of age in the old and middle-aged males in Pingliang area.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , China , Epidemiology , Erectile Dysfunction , Epidemiology , Mental Disorders , Epidemiology , Prevalence , Sexual Behavior , Sexual Dysfunctions, Psychological , Epidemiology , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>To study the polymorphism of c-Ha-ras 3' variable number of tandem repeat (VNTR) and its relationship with development of postmolar tumor.</p><p><b>METHODS</b>The cases of hydatidiform mole (HM) were retrospectively analyzed by amplified fragment length polymorphism-polyacrylamide gel electrophoresis. The DNA origin of HM was determined by comparison with the parents' DNA amplified results.</p><p><b>RESULTS</b>Among the samples from 15 cases, DNA from only paternal origin was found in 2 cases. DNA from both parents was in 13 cases, and of these 13 cases, 2 were found to be had balanced DNA origin, 11 had more DNA form paternal origin than DNA from maternal origin.</p><p><b>CONCLUSION</b>The HM which has DNA from both parents origin and predominantly from paternal origin developed to postmolar tumor more frequently.</p>