女贞子活性成分抗肝纤维化作用机制研究进展

肝纤维化为“肝病-肝纤维化-肝硬化/肝癌”的中间环节,存在于大部分肝病的发展过程中。有效逆转肝纤维化是防止其进一步发展的重要手段,但是目前还没有治疗肝纤维化的特效药,而女贞子Ligustri Lucidi Fructus作为一种天然药用植物,其活性成分具有抗肝纤维化功能。通过归纳梳理女贞子活性成分通过调控相关信号通路抗肝纤维化作用机制进行综述,为进一步对女贞子靶向治疗肝纤维化的研究提供理论参考。     

Comparison of the ex-vivo oral mucosal permeation of tryptophan-leucine (Trp-Leu) and its myristoyl derivative

The ex vivo permeation of a model peptide, tryptophan-leucine (Trp-Leu), was studied using two different regions of pig oral mucosa, the hard palate and the cheek. In order to increase the mucosal absorption of Trp-Leu, a lipophilic derivative was synthesized by acylation of the N-terminal amino group of Trp-Leu with myristic acid. The purified Trp-Leu derivative (Myr-Trp-Leu) was more lipophilic than the parent Trp-Leu as observed by HPTLC (R_f's values of 0.41 and 0.81, respectively). Measurement of partition coefficients in n-octanol/phosphate buffer pH 7.4, gave K_p values of −0.68 and 1.04 for Trp-Leu and Myr-Trp-Leu, respectively. The native Trp-Leu was unable to pass through the keratinized layer of palatal mucosa, and after 24 h only 12% had passed through the buccal mucosa to the receptor compartment. The higher lipophilicity of the acylated peptide, meant that it was not easily transported across the oral mucosal barrier but accumulated in the tissue, founding 25 and 70% of the original amount in the palatal and buccal mucosae, respectively. Both, Trp-Leu and Myr-Trp-Leu were found to be stable in palatal and buccal mucosae.     

Flagella are a positive predictor for virulence inLegionella

Pathogenesis of Legionnaires» disease is strictly related to the ability of the legionellae to infect phagocytic cells, yet surface markers of virulence inLegionellaisolates are currently unknown. Rabbit antibodies raised against purified flagella ofLegionella pneumophilaserogroup 1 recognized a total of 24 of 30 laboratory-maintained isolates ofL. pneumophilaserogroups 1–15 and 16 of 24 otherLegionellaspecies tested by rapid immunoblot and indirect immunofluorescence assay. All isolates possessing flagella detectable with these anti-flagella antibodies, regardless of species, were capable of infectingHartmannella vermiformis. Isolates lacking immunologic cross-reactivity were shown to lack purifiable flagella. The majority of aflagellate isolates were not motile and failed to multiply intracellularly in co-culture withHartmannella vermiformis. Some isolates characterized as aflagellate when harvested from BCYE agar were able to multiply in amoebae, and flagella were subsequently detectable by immunologic methods. These data suggest that lack of immunologic recognition of flagella in laboratory-maintained isolates ofLegionellais due to their attenuation and a corresponding loss of expression of flagella. More importantly, the presence of flagella can serve as a positive predictive marker for strain virulence and is useful in determining the virulence status ofLegionellaisolates.     

Influence of Nighttime Blood Pressure on Left Atrial Size in Uncomplicated Arterial Systemic Hypertension

The aim of the study was to determine the relations of 24-h blood pressure (BP) and its different phases with left atrial size. A total of 130 subjects (mean age 46 years) not taking cardiac drugs were studied by M-mode and Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into two groups: 25 normotensives and 105 hypertensives (history of antihypertensive treatment and office diastolic BP > 90 mm Hg). The two groups were comparable in terms of sex, age, and heart rate, whereas body mass index, (P < .01), office BP, average 24-h BP, and average daytime and nighttime BP (all P < .00001) were higher in hypertensives. Hypertensives also had increased left atrial dimension, left atrial dimension/aortic root ratio (both P < .001), and left ventricular mass (LV) indexed for height (P < .0001). Positive correlations of left atrial dimension were found with office BP, average 24-h, average daytime and nighttime systolic and diastolic BP, LV mass index, and Doppler-derived E/A ratio. In a multivariate model that included potentially confounding factors, only body mass index (standardized β coefficient = 0.41, P < .00001), average nighttime diastolic BP (β = 0.33, P < .00001), and male sex (β = 0.18, P < .01) were independent predictors of left atrial size in the pooled population. In conclusion, left atrial size is more closely related to ambulatory, rather than office, BP measurements, and high average nighttime BP is a powerful marker of left atrial enlargement in arterial hypertension.     

Screening asymptomatic adolescent males for chlamydia

Ninety-seven asymptomatic 16–21-year-old sexually active adolescent males were evaluated for gonorrhea and chlamydia by culture, chlamydia enzyme immunoassay, and an analysis of a random urine sample for pyuria using centrifuged urine and urine cytometer. The incidence of gonorrhea was 5.3% and chlamydia by culture 12.3%. Immunoassay was superior in sensitivity and specificity (75% and 99%, respectively) to centrifuged urine (sensitivity 58%, specificity 92%) or urine cytometer (58% and 91%) in identifying asymptomatic chlamydia urethritis. Chlamydia enzyme immunoassay is an acceptable, more rapid, and less expensive alternative to culture. The absence of pyuria in asymptomatic males cannot be assumed to indicate the absence of a sexually transmitted disease.     

Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke.Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033)

BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F.MethodsHealthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2–6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3.ResultsOverall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13 shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > −10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI −10.6).ConclusionIn Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series.Trial registration: ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.