Meta-analysis of changes in thiol-disulfide homeostasis during preeclampsia.

The present study systematically assessed alterations in thiol-disulfide homeostasis among women with preeclampsia (PE) through meta-analysis. This was conducted as such changes are believed to be associated with the oxidative stress underlying this condition. A comprehensive search of Medline, Web of Science, and Embase databases was conducted from their inception until 22 March 2023, to identify studies comparing levels of native thiol, total thiol, and disulfide between pregnant women with PE and those without PE. Results were pooled using a random-effects model to account for study heterogeneity. The analysis included a total of 631 women diagnosed with PE and 668 healthy pregnant women, encompassing 13 case-control studies and 1 prospective study. Pooled outcomes revealed that women with PE had significantly lower blood levels of native thiol, (mean difference [MD] -51.42 umol/L; 95% confidence interval [CI] -79.75 to -23.10 umol/L; P < 0.001; I2 = 0% and total thiol (MD -65.56 umol/L; 95% CI -104.97 to -26.15 umol/L; P = 0.001; I2 = 0%) compared to the control group. In contrast, no significant difference was observed in blood disulfide levels between the two groups (MD -1.10 umol/L; 95% CI -4.41 to -2.21 umol/L; P = 0.51; I2 = 0%). Subgroup analyses indicated that the results were consistent across studies matched by gestational age and body mass index, as well as those with varying quality scores (P for subgroup differences all > 0.05). In conclusion, women with PE are associated with significantly reduced blood levels of native and total thiols but show no change in blood disulfide levels, suggesting a state of reduced antioxidants in PE.

Polysaccharides from waste Zingiber mioga leaves: Ultrasonic-microwave-assisted extraction, characterization, antioxidant and anticoagulant potentials.

Zingiber mioga is a highly economic crop that is used to produce vegetables, spices and herbal pharmaceuticals. Its edible flower bud contributes most to the economic value, but the big leaves were discarded as agricultural waste, which urgently needs to be exploited. In this work, polysaccharides from waste Z. mioga leaves (PWZMLs) were extracted using ultrasonic-microwave-assisted extraction (UMAE). After purification and characterization, the antioxidation and anticoagulation of PWZMLs were evaluated to appraise the potential in cardiovascular protection. Under the liquid-solid ratio of 26: 1 mL/g, after ultrasonication at 495 W for 10 min, followed by microwaving at 490 W for 5 min, the yield of PWZMLs achieved to 6.22 ± 0.14 %, notably higher (P < 0.01) than other methods, and ultrasound contributed more to the yield than microwave. Various analyses confirmed that PWZMLs were negatively charged polysaccharides with galacturonic acid the dominant uronic acid. PWZMLs exerted excellent antioxidant capacity, especially for scavenging 1, 1-diphenyl-2-picrylhydrazyl radical. PWZMLs also elicited promising anticoagulant property, particularly for prolonging activated partial thromboplastin time and lowering fibrinogen, which were almost equivalent to heparin at the same concentration. PWZMLs contained two polysaccharide fractions (199.53 and 275.42 kDa) that could synergistically contribute to the pronounced antioxidant and anticoagulant activities. The PWZMLs extracted with optimized UMAE have great potential in cardiovascular protection.

First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.

BACKGROUND: QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. METHODS: In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. RESULTS: Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. CONCLUSIONS: QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.

The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.

The clinical benefits of targeting programmed death-ligand 1 (PD-L1) in various cancers represent a strategy for the treatment of immunosuppressive diseases. Here, it was demonstrated that the expression levels of PD-L1 in cells were greatly upregulated in response to H1N1 influenza A virus (IAV) infection. Overexpression of PD-L1 promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes. Moreover, the association between PD-L1 and Src homology region-2, containing protein tyrosine phosphatase (SHP2), during IAV/H1N1 infection was analyzed by employing the SHP2 inhibitor (SHP099), siSHP2, and pNL-SHP2. The results showed that the expressions of PD-L1 mRNA and protein were decreased under SHP099 or siSHP2 treatment, whereas the cells overexpressing SHP2 exhibited the opposite effects. Additionally, the effects of PD-L1 on the expression of p-ERK and p-SHP2 were investigated in PD-L1-overexpressed cells following WSN or PR8 infection, determining that the PD-L1 overexpression led to the decreased expression of p-SHP2 and p-ERK induced by WSN or PR8 infection. Taken together, these data reveal that PD-L1 could play an important role in immunosuppression during IAV/H1N1 infection; thus, it may serve as a promising therapeutic target for development of novel anti-IAV drugs.

5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4.

Keloids display many cancerous properties, including uncontrolled and invasive growth, high rates of recurrence as well as similar bioenergetics. 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that performs cytotoxic effects by producing reactive oxygen species (ROS), which is linked to lipid peroxidation and ferroptosis. Herein, we explored underlying mechanisms of 5-ALA-PDT against keloids. We identified that 5-ALA-PDT led to elevated levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which are associated with anti-oxidation effects and ferroptosis inhibition. These results may indicate that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thus promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.

RGC-32 facilitates pancreatic cancer via activating Wnt/ß-catenin signaling.

Longitudinal studies have indicated the facilitating effect of RGC-32 during diverse disease progression including pancreatic cancer, yet the systematic and detailed effect of RGC-32 during pancreatic cancer is largely unknowable. For this purpose, we took advantage of the pancreatic cancer cell line (BXPC3) with RGC-32 expression and then modulated its expression by lentivirus-mediated knockdown (shRGC-32) and overexpression (pcDNA-RGC-32). To verify the effect of Wnt/ß-catenin signaling in RGC-32-based tumorigenicity, we added the agonist CT99021 to the shRGC-32 BXPC3 cell line and pancreatic cancer mouse model. The deficiency in cellular vitality (cell survival, apoptosis, cell cycle) and migration of BXPC3 were sharply rescued by shRGC-32 in vitro. Notably, the aforementioned phenotypes as well as the expression pattern of EMT-associated biomarkers of BXPC3 with shRGC-32 expression could largely rescued by the agonist of Wnt/ß-catenin in vitro and in vivo. Our data indicated the facilitating effect of RGC-32 upon pancreatic cancer cell line and mouse model via activating the Wnt/ß-catenin signaling, which collectively suggested the feasibility of RGC-32 as a potent diagnostic and therapeutic target of pancreatic cancer in the future.

Mrz1, a Novel Mitochondrial Outer Membrane RING Finger Protein, is Degraded Through the Ubiquitin-Proteasome Pathway in Schizosaccharomyces pombe.

The RING (Really Interesting New Gene) finger proteins are a large diverse group of Zinc finger proteins. Many determined RING finger proteins are ubiquitin-protein E3 ligases and RING E3s are the most abundant type of ubiquitin ligase. RING finger and RING finger E3s have been discovered in many organisms where they play various functions, including DNA repair, ubiquitination and mitochondrial protein quality control. In this study, we identified a novel mitochondrial protein (SPBC16G5.03) with predicted RING finger domain within an N-terminal 21-60 amino acids and named it Mrz1 (mitochondrial RING finger protein). Our results showed that Mrz1 is localized in the mitochondrial outer membrane. Deletion of mrz1 did not affect cell growth in an unstressed state, but increases sensitivity to selenite. We showed that Mrz1 was degraded during the stationary phase and blocked by addition proteasome inhibitor MG132. We further showed that the E2 enzyme Ubc13 was identified among 8 candidate proteins as the ubiquitin-conjugating enzyme in this system. These data suggested that the Mrz1 was degraded likely through the ubiquitin-proteasome system.

Comparison of case-based learning combined with Rain Classroom teaching and traditional method in complete denture course for undergraduate interns.

BACKGROUND: Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice. OBJECTIVE: This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns. METHODS: In a course called "Problems and treatment strategies of complete denture after wearing", interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns' feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher's exact test were used for statistical analysis in this study. RESULTS: The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode. CONCLUSION: Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.

Microwave-Assisted Enzymatic Extraction, Partial Characterization, and Antioxidant Potential of Polysaccharides from Sagittaria trifolia Tuber.

Sagittaria trifolia tuber is an aquatic vegetable. In this work, microwave-assisted enzymatic extraction (MEE) was used to extract S. trifolia tuber polysaccharides (STTPs). Optimum conditions were complex enzyme of 2 %, liquid-to-solid ratio of 43 : 1 mL g-1 , microwave power of 506 W, and time of 8 min, under which STTPs yield was 36.22±0.69 %, higher than those of other methods. STTPs were sulfated polysaccharides with sulfur valence of S6+ . STTPs comprised mannose, glucose, galactose, and arabinose at a mole ratio of 3.69 : 19.33 : 6.21 : 1.00, molecular weights of 3606 kDa and 149.6 kDa, particle size of 220 nm, and zeta potential of -5.02 mV. The surface of STTPs was full of bumps and holes, and abundant in O1s and non-functionalized C1s. STTPs would scavenge reactive oxygen species with advantage. It would provide an efficient MEE method to obtain antioxidant STTPs, also a clue for extracting polysaccharides from starch-rich crops.

Cysteine Donor-Based Brain-Targeting Prodrug: Opportunities and Challenges.

Overcoming blood-brain barrier (BBB) to improve brain bioavailability of therapeutic drug remains an ongoing concern. Prodrug is one of the most reliable approaches for delivering agents with low-level BBB permeability into the brain. The well-known antioxidant capacities of cysteine (Cys) and its vital role in glutathione (GSH) synthesis indicate that Cys-based prodrug could potentiate therapeutic drugs against oxidative stress-related neurodegenerative disorders. Moreover, prodrug with Cys moiety could be recognized by the excitatory amino acid transporter 3 (EAAT3) that is highly expressed at the BBB and transports drug into the brain. In this review, we summarized the strategies of crossing BBB, properties of EAAT3 and its natural substrates, Cys and its donors, and Cys donor-based brain-targeting prodrugs by referring to recent investigations. Moreover, the challenges that we are faced with and future research orientations were also addressed and proposed. It is hoped that present review will provide evidence for the pursuit of novel Cys donor-based brain-targeting prodrug.

Peptidomic Analysis on Mouse Lung Tissue Reveals AGDP as a Potential Bioactive Peptide against Pseudorabies Virus Infection.

Pseudorabies virus (PRV) infection could cause severe histopathological damage via releasing multiple factors, including cytokines, peptides, etc. Here, peptidomic results showed that 129 peptides were identified in PRV-infected mouse lungs and were highly involved in the process of PRV infection. The role of one down-regulated biological peptide (designated as AGDP) during PRV infection was investigated. To verify the expression profiles of AGDP in response to PRV infection, the expression level of the precursor protein of AGDP mRNA was significantly decreased in PRV-infected mouse lungs and cells. The synthesized AGDP-treating cells were less susceptible to PRV challenges than the controls, as demonstrated by the decreased virus production and gE expression. AGDP not only inhibited the expression of TNF-α and IL-8 but also appeared to suppress the extracellular release of high-mobility group box 1 (HMGB1) by inhibiting the output of nuclear HMGB1 in cells. AGDP could also inhibit the degradation of IκBα and the phosphorylation levels of P65 after PRV infection. In total, our results revealed many meaningful peptides involved in PRV infection, thereby enhancing the current understanding of the host response to PRV infection, and how AGDP may serve as a promising candidate for developing novel anti-PRV drugs.

Neuropeptide S and its receptor NPSR enhance the susceptibility of hosts to pseudorabies virus infection.

The neuropeptide S (NPS) and its receptor (NPSR) represent a signaling system in the brain. Increased levels of NPS and NPSR have been observed in PK15 cells and murine brains in response to pseudorabies virus (PRV) infection, but it remains unclear whether elevated levels of NPS and NPSR are involved in the pathogenic process of PRV infection. In this study, the activities of both NPS and NPSR during PRV pathogenesis were explored in vitro and in vivo by reverse transcription polymerase chain reaction (RT-PCR), PCR, real-time quantitative RT-PCR (qRT-PCR), qPCR, TCID50, and Western blotting methods. NPSR-deficient cells were less susceptible to PRV infection, as evidenced by decreased viral production and PRV-glycoprotein E (gE) expression. In vitro studies showed that exogenous NPS promoted the expression of interleukin 6 (IL-6) mRNA but inhibited interferon ß (IFN-ß) mRNA expression in PK15 cells after PRV infection. In vivo studies showed that NPS-treated mice were highly susceptible to PRV infection, with decreased survival rates and body weights. In addition, NPS-treated mice showed elevated levels of IL-6 mRNA and STAT3 phosphorylation. However, the expression of IFN-ß mRNA was greatly decreased after virus challenge. Contrasting results were obtained from the NPSR-ir-treated groups, which further highlighted the effects of NPS. This study revealed that NPS-treated hosts are more susceptible to PRV infection than controls. Moreover, excessive IL-6/STAT3 and defective IFN-ß responses in NPS-treated mice may contribute to the pathogenesis of PRV.

Eleocharis dulcis corm: phytochemicals, health benefits, processing and food products.

Eleocharis dulcis, an aquatic plant belonging to Cyperaceae family, is indigenous to Asia, and also occurs in tropical Africa and Australia. The edible corm part of E. dulcis is a commonly consumed aquatic vegetable with a planting area of 44.46 × 103 hm2 in China. This work aims to explore the potential of E. dulcis corm for use as a new food source for sufficient nutrients and health benefits by reviewing its nutrients, phytochemicals, functions, processing and food products. Eleocharis dulcis corm contains starches, dietary fibers, non-starch polysaccharides, proteins, amino acids, phenolics, sterols, puchiin, saponins, minerals and vitamins. Among them, phenolics including flavonoids and quinones could be the major bioconstituents that largely contribute to antioxidant, anti-inflammatory, antibacterial, antitumor, hepatoprotective, neuroprotective and hypolipidemic functions. Peel wastes of E. dulcis corm tend to be enriched in phenolics to a much higher extent than the edible pulp. Fresh-cut E. dulcis corm can be consumed as a ready-to-eat food or processed into juice for beverage production, and anti-browning processing is a key to prolonging shelf life. Present food products of E. dulcis corm are centered on various fruit and vegetable beverages, and suffer from single categories and inadequate development. In brief, underutilized E. dulcis corm possesses great potential for use as a new food source for sufficient nutrients and health benefits. © 2021 Society of Chemical Industry.

A modified urinary catheterisation technique to reduce urine leakage: A prospective randomised study.

BACKGROUND: Long-term indwelling catheters assist people who are unable to use another bladder management method. However, urine leakage is a common problem with an indwelling urinary catheter. This study aims to determine whether a modified catheterisation technique would reduce urine leakage incidence. METHODS: Participants were randomly divided into conventional or modified catheterisation groups. In the modified technique group, the volume of fluid that needed to be injected into the balloon to obtain a suitable catheter front-end curvature (120-145°) was measured before catheterisation. Baseline characteristics and first-time success rates and procedure durations were similar between groups. RESULTS: There were 30 patients in each group. Compared with conventional catheterisation, the modified catheterisation group had smaller residual urine volume (median 11 mL Vs. 30.5 mL, p<0.001) and more leakage-free days (30 days Vs. 10 days, p<0.001). Leakage-free survival was longer in the modified catheterisation group (p<0.001). The residual urine volume (>17 vs ≤17 ml (median); incident rate ratio (IRR), 28.710; 95%CI, 4.114-200.331; p=0.001) was independently associated with urine leakage. CONCLUSIONS: The modified catheterisation technique may reduce the incidence of urine leakage.

Comparison of the effect of fluticasone combined with salmeterol and fluticasone alone in the treatment of pediatric asthma.

INTRODUCTION: A systematic review and meta-analysis was performed to investigate the effect of fluticasone + salmeterol and fluticasone alone in the treatment of pediatric asthma. EVIDENCE ACQUISITION: Studies meeting specific selection criteria were selected from online databases, including Pubmed, Embase, and the Cochrane Library. The quality of randomized controlled trials was assessed using the Cochrane Library. Weighted mean difference (WMD) and 95% CI were used to evaluate the effect size of continuous variables, while rate ratio (RR) and 95% CI were used for dichotomous variables. EVIDENCE SYNTHESIS: A total of 11 studies, including 8272 pediatric asthma patients, were included in this meta-analysis. Among these, 4133 patients were in the salmeterol + fluticasone group. The changes in forced expiratory volume in 1 second in children with asthma in the salmeterol + fluticasone and fluticasone alone groups were significantly different (fixed effects model, WMD=3.26, 95% CI: 1.52-5.00, P=0.0002). Asthma exacerbation between two groups were significantly different (fixed effects model, RR=0.85, 95% CI: 0.73-0.98, Z=2.18, P=0.03). There was no difference in the incidence of adverse events between salmeterol + fluticasone and fluticasone alone in the treatment of pediatric asthma (P>0.05). When the control group was treated with double dose fluticasone, the difference of changes in FEV1 and asthma exacerbation in children with asthma between the two groups was not significant. CONCLUSIONS: The efficacy of salmeterol + fluticasone is better than fluticasone alone, and the efficacy of salmeterol + fluticasone is equal to doubling the dose of fluticasone in the treatment of pediatric asthma.

Maternal fever during preconception and conception is associated with congenital heart diseases in offspring: An updated meta-analysis of observational studies.

BACKGROUNDS: Many studies have evaluated the effect of maternal fever on the development risk of congenital heart diseases (CHDs) in offspring, but the findings were inconsistent. Furthermore, a complete overview of the existing data was also missing. Therefore, we intend to provide updated epidemiologic evidence to estimate the association between maternal fever and the risk of overall CHDs and specific CHD phenotypes in offspring. METHODS: Pubmed, Embase, and Web of Science were searched through March 2020 to identify eligible studies that assessed the association between maternal fever and CHDs risk in offspring. The summary risk estimates were calculated using random-effects models. Potential heterogeneity source was explored by subgroup analyses and potential publication bias was assessed by Begg funnel plots and Begg rank correlation test. RESULTS: Sixteen studies involving 31,922 CHDs cases among 183,563 participants were included in this meta-analysis. Overall, mothers who had a fever experience during preconception and conception periods had a significantly higher risk of overall CHDs in offspring (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.21-1.73) when compared with those who did not have a fever experience. For specific CHD phenotypes in offspring, a statistically significant association was found between maternal fever and risk of conotruncal defects (CTD) (OR = 1.38, 95%CI: 1.01-1.89), atrial septal defects (ASD) (OR = 1.48, 95% CI: 1.01-2.17), transposition of the great vessels (TGA) (OR = 1.81, 95% CI: 1.14-2.88), and right ventricular outflow tract obstruction (RVOTO) (OR = 1.66, 95% CI: 1.04-2.65). Relevant heterogeneity moderators have been identified by subgroup analyses, and sensitivity analyses yielded consistent results. CONCLUSIONS: Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, our review indicates that maternal fever is significantly associated with the risk of CHDs in offspring, which highlights that preventing maternal fever during the preconception and conception periods play an important role in decreasing the risk of CHDs in offspring. However, given the limited number of current case-control studies, larger-sample prospective studies are required to further confirm our results. Besides, due to the underlying mechanisms between maternal fever and the risk of specific CHD phenotypes in offspring are still unreported, more research is needed to explore the possible mechanisms.

Sagittaria trifolia tuber: bioconstituents, processing, products, and health benefits.

Sagittaria trifolia is an aquatic plant that is distributed worldwide. The edible tuber part of S. trifolia is a very common and popular vegetable in China. The aim of the present review is to discuss the discovery of nutraceuticals from S. trifolia tuber by reviewing its major constituents, food processing, food products, and health-promoting benefits. Sagittaria trifolia tuber comprises a series of nutritional and bioactive constituents, including dietary fibers, amino acids, minerals, starches, non-starch polysaccharides, diterpenoids, colchicine, phenols, and organic acids. Food processing affects its flavor, biocomponents, and bioactivity. Numerous S. trifolia tuber-based food products and nutraceuticals have been developed, but new categories of products and the anticipated functions still need to be explored. The non-starch polysaccharides could be the central ingredients that contribute to the plant's antioxidant, hepatoprotective, hypoglycemic, lipid-regulating, and immunostimulatory properties. Of these, antioxidant and hepatoprotective effects have been thoroughly investigated. Procedures for the extraction and purification of polysaccharides influence their health-promoting actions. Overall, S. trifolia tuber is an underutilized aquatic vegetable species that is an emerging subject for nutraceutical research. © 2020 Society of Chemical Industry.

Effects of ALA-PDT on the Healing of Mouse Skin Wounds Infected With Pseudomonas aeruginosa and Its Related Mechanisms.

Photodynamic therapy (PDT) is a promising new method to eliminate microbial infection and promote wound healing. Its effectiveness has been confirmed by some studies; however, the mechanisms of PDT in wound healing remain obscure. We used mouse skin wounds infected with Pseudomonas aeruginosa as a research object to explore the therapeutic effects and mechanisms of 5-aminolevulinic acid photodynamic therapy (ALA-PDT). ALA-PDT treatment significantly reduced the load of P. aeruginosa in the wound and surrounding tissues and promoted the healing of skin wounds in mice. Hematoxylin-eosin (HE) and Sirius red staining showed that ALA-PDT promoted granulation tissue formation, angiogenesis, and collagen regeneration and remodeling. After ALA-PDT treatment, the expression of inflammatory factors (TNF-α and IL-1ß) first increased and then decreased, while the secretion of growth factors (TGF-ß-1 and VEGF) increased gradually after treatment. Furthermore, ALA-PDT affected the polarization state of macrophages, activating and promoting macrophages from an M1 to an M2 phenotype. In conclusion, ALA-PDT can not only kill bacteria but also promote wound healing by regulating inflammatory factors, collagen remodeling and macrophages. This study further clarifies the mechanism of PDT in the healing of infectious skin wounds and provides further experimental evidence for its clinical treatment of skin wounds infected by P. aeruginosa.

The consistency of an optical body surface scanning method compared with computed tomography: a validation study.

OBJECTIVE: The ideal noninvasive method for evaluation of pectus excavatum remains to be defined. We sought to verify the accuracy of an optical body surface scanning method compared with conventional CT scan. MATERIALS AND METHODS: A PrimeSense 3D sensor was used to obtain data from patients undergoing surgical or noninvasive treatment for pectus excavatum. The Haller index, external Haller index, and depth ratio were then calculated from both body scan and computed tomography scan data for the same patients. Statistical analyses were carried out to find if there is consistency between data from body scanning and computed tomography. RESULTS: Data acquisition was complete. In total, 40 patients (median age: 5.03 years, 11 female) with pectus excavatum undergoing nonoperative (n = 13) or surgical Nuss treatment (n = 27) were included. The Haller index was lower in vacuum bell patients, which also had a higher female proportion. Pearson correlation coefficient between external Haller indices from body scanning and from computed tomography and between the depth ratios from body scanning and from computed tomography were 0.63 and 0.84, respectively. By intraclass correlation coefficient method, the correlation coefficient was 0.56 between external Haller indices from body scanning and from computed tomography and 0.80 between depth ratios from body scanning and from computed tomography. CONCLUSION: The optical body surface scanning is a reliable approach to the measurement of PE severity and could be routinely used in the monitoring of PE development of treatment, especially in the pediatric population. STUDY TYPE: Diagnostic test. LEVEL OF EVIDENCE: Level II.

Role of neuromedin B and its receptor in the innate immune responses against influenza A virus infection in vitro and in vivo.

The peptide neuromedin B (NMB) and its receptor (NMBR) represent a system (NMB/NMBR) of neuromodulation. Here, it was demonstrated that the expression of NMBR in cells or murine lung tissues was clearly upregulated in response to H1N1/PR8 influenza A virus infection. Furthermore, the in vitro and in vivo activities of NMB/NMBR during PR8 infection were investigated. It was observed that A549 cells lacking endogenous NMBR were more susceptible to virus infection than control cells, as evidenced by the increased virus production in the cells. Interestingly, a significant decrease in IFN-α and increased IL-6 expression were observed in these cells. The role of this system in innate immunity against PR8 infection was probed by treating mice with NMB. The NMB-treated mice were less susceptible to virus challenge, as evidenced by increased survival, increased body weight, and decreased viral NP expression compared with the control animals. Additionally, the results showed that exogenous NMB not only enhanced IFN-α expression but also appeared to inhibit the expression of NP and IL-6 in PR8-infected cells and animals. As expected, opposing effects were observed in the NMBR antagonist-treated cells and mice, which further confirmed the effects of NMB. Together, these data suggest that NMB/NMBR may be an important component of the host defence against influenza A virus infection. Thus, these proteins may serve as promising candidates for the development of novel antiviral drugs.