Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM2.5 components.

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.

Capsaicin: A Novel Approach to the Treatment of Functional Dyspepsia.

Capsaicin, the principal spicy component of red pepper, shows numerous bioactivities these years. Based on the results of past studies, capsaicin may have potential effects on the treatment of functional dyspepsia (FD). However, most studies mainly investigate functional dyspepsia-treatment effects of capsaicin by discussing the relationship between capsaicin and transient receptor potential vanilloid type 1 (TRPV1). In fact, capsaicin may relieve the symptoms of FD in various ways. These effects involve desensitizing C nociceptive fibers, regulating kinds of neurotransmitters, counteracting viruses and inflammation, balancing the gut microbiota, inhibiting the secretion of gastric acid, and reducing oxidative stress damage. A full understanding of these mechanisms will help further development and utilization of capsaicin in food and medical fields.

Impact of Helicobacter pylori Infection and Outcome of Anti-Helicobacter pylori Therapy in Patients with Reflux Laryngopharyngitis.

Objectives: This study was designed to explore the relationship between Helicobacter pylori (Hp) infection and reflux laryngopharyngitis (RLP) and to evaluate the outcome of anti-Hp therapy in improving RLP symptoms. Methods: A total of 410 patients with RLP were enrolled and tested for Hp infection. The association of Hp infection with reflux symptom index (RSI) and reflux finding score (RFS) was determined. Hp-positive patients received either a proton pump inhibitor (PPI) omeprazole alone (control group) or a combination regimen (experimental group) consisting of omeprazole, mosapride citrate, amoxicillin, and clarithromycin. Therapeutic outcomes were compared 4 weeks later. Results: Of the 410 participants, 290 were Hp-positive and 120 Hp-negative. Both RSI and RFS were significantly higher in Hp-positive patients than in Hp-negative patients. Hp infection status was positively correlated with RSI (P < 0.05) and RFS (P < 0.05). The overall response rate was higher in the experimental group than in the control group. Both the groups had a significant reduction in RSI and RFS after therapy, with a greater improvement in the experimental group (P < 0.05). Conclusion: Our findings establish a link between Hp infection and RLP. Anti-Hp therapy improves RSI and RFS in RLP patients. Therefore, Hp eradication drugs may be added to the PPI-based regimen in the treatment of RLP.

Toxin-Enabled "On-Demand" Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin-Resistant Staphylococcus aureus Infection.

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

The effects of thermal treatment on emulsifying properties of soy protein isolates: Interfacial rheology and quantitative proteomic analysis.

In this work, the interfacial rheological properties and the quantitative changes of proteins at interfacial protein layers of emulsions stabilized by soy protein isolates (SPI) and heat-treated soy protein isolates (HSPI) were investigated. The quantification results showed that the relative quantities of albumin (2S) and glycinin (11S) in SPI decreased at the oil-water interface, suggesting that they possessed lower interfacial affinities at the interface. Basic 7S globulin presented more adsorption at the oil-water interface due to the well balance of the hydrophobic and hydrophilic groups of its amino acid sequence. The HSPI (95 °C, 20 min) showed a larger apparent diffusion rate (Kdiff) and a shorter equilibrium adsorption time. The results of interfacial rheology of globulins were consistent with their interfacial quantitative changes, which demonstrated that the interfacial behavior and adsorption ability of globulin were improved by thermal treatment. In this research, the interfacial behaviors of SPI and HSPI was illustrated by their interfacial properties and quantitative results of interfacial adsorbed protein layers, would promote a profound comprehension for the interfacial behavior of the protein and the influence of thermal treatment on protein interfacial properties.

Role of green tea nanoparticles in process of tea cream formation - A new perspective.

Green tea nanoparticles (gTNPs) are considered as the precursors of tea cream, while the role of gTNPs in the process of tea cream formation remains obscure. This study indicated that gTNPs could be coated with epigallocatechin gallate (EGCG)-caffeine (CAF) complexes to form a ternary aggregate participating in tea cream formation. First, the ζ-potentials of gTNPs and EGCG-CAF complexes were adjusted by charge screening. Then, gTNPs were introduced into EGCG + CAF mixture solutions under different ζ-potential conditions to examine their effect on turbidity, particle size and components of mixture solutions. Finally, isothermal titration calorimetry (ITC) was applied to investigate the influence of gTNPs on the thermal effects of the interaction between EGCG and CAF. Our results reveal that hydrophobic interaction exceeded electrostatic repulsion to dominate the interaction between gTNPs and EGCG-CAF complexes at the low ζ-potential condition, thus forming the gTNPs/EGCG/CAF ternary aggregate.

Micromotors for Active Delivery of Minerals toward the Treatment of Iron Deficiency Anemia.

As the most common nutritional disorder, iron deficiency represents a major public health problem with broad impacts on physical and mental development. However, treatment is often compromised by low iron bioavailability and undesired side effects. Here, we report on the development of active mineral delivery vehicles using Mg-based micromotors, which can autonomously propel in gastrointestinal fluids, aiding in the dynamic delivery of minerals. Iron and selenium are combined as a model mineral payload in the micromotor platform. We demonstrate the ability of our mineral-loaded micromotors to replenish iron and selenium stores in an anemic mouse model after 30 days of treatment, normalizing hematological parameters such as red blood count, hemoglobin, and hematocrit. Additionally, the micromotor platform exhibits no toxicity after the treatment regimen. This proof-of-concept study indicates that micromotor-based active delivery of mineral supplements represents an attractive approach toward alleviating nutritional deficiencies.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

OBJECTIVE: To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). BACKGROUND: The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. MATERIALS AND METHODS: Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. RESULTS: Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. CONCLUSIONS: Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Shorter Treatment Intervals of East Asians with Port-Wine Stain with Pulsed Dye Laser Are Safe and Effective-A Prospective Side-by-Side Comparison.

OBJECTIVE: To compare the safety and efficacy of pulsed dye laser (PDL) at different intervals for the treatment of East Asians with Port-Wine Stain (PWS). BACKGROUND: The population of East Asians around the world is about 1.6 billion, and they are considered to have more melanin in their skin compared with Caucasians. Nevertheless, no studies about the optimal treatment intervals for East Asians with PWS have been carried out. METHODS: We prospectively investigated 39 East Asian patients with untreated PWS. Half of the PWS lesion was randomly allocated to be treated at 3 weeks and the other half at 6 weeks. Both halves of the PWS were treated three times in total. The efficacy outcome 2 months post final treatment was evaluated by visual and chromameter evaluation. RESULTS: The average blanching rate was 40.27% and 44.17% for PDL treatments at the 3- and 6-week interval sites, respectively (p > 0.05). No patient developed scarring or permanent pigmentation change. LIMITATIONS: There was no age criteria involved in the enrollment of patients in this study. Additionally, there is no comparison with long-term treatments at different intervals. CONCLUSIONS: PDL treatment at 3-week interval proved to be safe for East Asians with PWS. This can reduce the total duration of the course of treatments and had no increase in side effects compared with the standard interval treatments.

In Vivo Investigation of the Safety and Efficacy of Pulsed Dye Laser with Two Spot Sizes in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison.

OBJECTIVE: Pulsed dye laser (PDL) with 7 and 10 mm spot sizes is widely used on a regular basis for the treatment of port-wine stain (PWS). BACKGROUND DATA: No studies have reported on the differences in efficacy outcomes resulting from the use of different laser spot sizes in the treatment of PWS by PDL. Thus, an in vivo investigation into the differences in safety and efficacy of treatment between two spot sizes (7 vs. 10 mm) of PWS by PDL was conducted. MATERIALS AND METHODS: A total of 35 PWS patients underwent three treatment sessions by using a 595 nm wavelength PDL (Vbeam®, Candela Corp) with two laser settings: (1) 7 mm spot size, radiant exposure of 12 J/cm2 and (2) 10 mm spot size, radiant exposure of 10 J/cm2. Cryogen spray cooling and 1.5 msec pulse duration were applied. Therapeutic outcomes were evaluated by visual and chromametric evaluation 3 months after the final treatment. RESULTS: Average blanching rates were 34.03% and 36.51% at sites treated by PDL with 7 and 10 mm laser spot sizes, respectively (p < 0.05). CONCLUSIONS: On the basis of the laser setting, the therapeutic outcomes of PDL with 7 and 10 mm spot sizes were similar. PDL with a 10 mm laser spot size is more efficacious with lower radiant exposure than PDL with a 7 mm spot size; it can also reduce the treatment time.

Construction of pH-sensitive lysozyme/pectin nanogel for tumor methotrexate delivery.

Novel nano-particles were developed from lysozyme-pectin through self-assembly, and the nanogels could be used as a carrier for the antitumor agent, methotrexate (MTX). The nanogels exhibited spherical with diameters about 109 ± 2 nm and narrow particle size distribution, as well as negative surface charge. Furthermore, the particle size and morphology of the nanogels hardly changed with the incorporation of MTX. The loading capacity of MTX in nanogels could reach 17.58 ± 0.85%. MTX-loaded nanogels were pH-dependent, accelerated release of MTX at a decreasing pH from 7.4 to 5.3. The MTT assay indicated that encapsulated MTX exhibited higher anticancer activity than free MTX. Meanwhile, MTX-loaded nanogels could be effectively endocytosed by HepG2 cells, resulting in enhanced cancer-cell apoptosis comparing to free MTX. It indicated that the nanogels had good biocompatibility and low toxicity. The obtained nanogels had great potential in the development of a new nanocarrier for anti-cancer drug delivery.

Antitumor activity of the protein and small molecule component fractions from Agrocybe aegerita through enhancement of cytokine production.

A water soluble extract from the medicinal mushroom Agrocybe aegerita has been shown to stimulate splenocyte proliferation, cytotoxic activity, and tumor rejection effect in tumor-bearing mouse models. In the present study, the crude extract was separated into a protein component fraction (Yp), mainly containing lectins and serine proteinase, and a small molecule component fraction (Ys), mainly containing triethylene glycol, α-bisabolol, n-hexadecanoic acid, and so on. The antitumor activity of the fractions was investigated in a tumor-bearing BALB/c mouse model. Repeat administration of Yp and Ys significantly inhibited tumor growth (P<.001), but little toxicity was observed. Moreover, the protein fraction Yp performed better than Ys in both antitumor and lifespan-prolonging activity. The cytokine expression levels in serum and splenocytes from extract-treated mice were selectively screened by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, and the results showed that Yp upregulated the mRNA level of Th2 cytokine interleukin-10 (P<.01), and Ys increased the mRNA level of granulocyte-macrophage colony-stimulating factor (P<.01) and anti-inflammatory cytokine transforming growth factor-ß (P<.01). All these data suggest that Yp and Ys can inhibit tumor growth via different mechanisms, which promotes the understanding of antitumor properties of medicinal fungi.

Inhibition of Epstein-Barr virus lytic cycle by an ethyl acetate subfraction separated from Polygonum cuspidatum root and its major component, emodin.

Polygonum cuspidatum is widely used as a medicinal herb in Asia. In this study, we examined the ethyl acetate subfraction F3 obtained from P. cuspidatum root and its major component, emodin, for their capacity to inhibit the Epstein-Barr virus (EBV) lytic cycle. The cell viability was determined by the MTT [3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide] method. The expression of EBV lytic proteins was analyzed by immunoblot, indirect immunofluorescence and flow cytometric assays. Real-time quantitative PCR was used to assess the EBV DNA replication and the transcription of lytic genes, including BRLF1 and BZLF1. Results showed that the F3 and its major component emodin inhibit the transcription of EBV immediate early genes, the expression of EBV lytic proteins, including Rta, Zta, and EA-D and reduces EBV DNA replication, showing that F3 and emodin are potentially useful as an anti-EBV drug.

Genome-wide transcriptome and proteome analysis on different developmental stages of Cordyceps militaris.

BACKGROUND: Cordyceps militaris, an ascomycete caterpillar fungus, has been used as a traditional Chinese medicine for many years owing to its anticancer and immunomodulatory activities. Currently, artificial culturing of this beneficial fungus has been widely used and can meet the market, but systematic molecular studies on the developmental stages of cultured C. militaris at transcriptional and translational levels have not been determined. METHODOLOGY/PRINCIPAL FINDINGS: We utilized high-throughput Illumina sequencing to obtain the transcriptomes of C. militaris mycelium and fruiting body. All clean reads were mapped to C. militaris genome and most of the reads showed perfect coverage. Alternative splicing and novel transcripts were predicted to enrich the database. Gene expression analysis revealed that 2,113 genes were up-regulated in mycelium and 599 in fruiting body. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to analyze the genes with expression differences. Moreover, the putative cordycepin metabolism difference between different developmental stages was studied. In addition, the proteome data of mycelium and fruiting body were obtained by one-dimensional gel electrophoresis (1-DGE) coupled with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nESI-LC-MS/MS). 359 and 214 proteins were detected from mycelium and fruiting body respectively. GO, KEGG and Cluster of Orthologous Groups (COG) analysis were further conducted to better understand their difference. We analyzed the amounts of some noteworthy proteins in these two samples including lectin, superoxide dismutase, glycoside hydrolase and proteins involved in cordycepin metabolism, providing important information for further protein studies. CONCLUSIONS/SIGNIFICANCE: The results reveal the difference in gene expression between the mycelium and fruiting body of artificially cultivated C. militaris by transcriptome and proteome analysis. Our study provides an effective resource for the further developmental and medicinal research of this promising fungus.