Targeting upregulation of the immunosuppressive activity of MDSCs with indirubin as a novel strategy to alleviate psoriasis.

BACKGROUND: Psoriasis is a chronic and incurable skin disorder that causes inflammation. There is an urgent clinical need for new treatments. We identified the natural compound indirubin as a potential potent agent for the treatment of psoriasis, but it's therapeutic effect and underlying mechanisms were not well understood. METHODS: Peripheral blood and skin tissues from psoriasis patients and healthy individuals were collected. Bioinformatics analysis was performed to investigate LAT1 expression and associated signal pathways in psoriasis skin lesions. A mouse model of psoriasis was established. Indirubin was administered separately or in combination with MDSCs depletion or adoptively transferred MDSCs. JPH203, rapamycin, siRNA, and NV5138 were further used to investigate the potential mechanism by which indirubin regulates MDSCs. RESULTS: Psoriasis patients had increased numbers of MDSCs in their blood and skin lesions, with high expression of Lat1. The upregulation of LAT1 expression and the arginine synthesis pathway was observed in psoriasis skin lesions. The number of MDSCs was increased, while their inhibitory effect on psoriatic T cells was decreased. Indirubin decreased Lat1 expression on the surface of MDSCs, inhibited mTOR pathway activation, upregulated Arg1 expression in MDSCs, and enhanced the immunosuppressive activity of MDSCs while inhibiting CD4+CCR6+ T cells. CONCLUSION: This study demonstrates indirubin's pharmacological and therapeutic effects, providing a basis for future clinical application in treating psoriasis.

Effects of arteriovenous fistulas and central venous catheters on the cardiac function and prognosis of patients on maintenance hemodialysis.

Objective: To investigate the effects of arteriovenous fistulas (AVFs) and central venous catheters (CVCs) on the left ventricular function (LVF) and prognosis of maintenance hemodialysis (MHD) patients. Methods: This retrospective cohort study included 270 patients (139 with AVF and 131 with CVC) undergoing dialysis with newly established vascular access in the blood purification center of Nanhua hospital, University of South China, from January 2019 to April 2021. Dialysis efficiencies, LVF indexes, and one-year prognoses were compared. Results: At six and twelve months after the establishment of vascular access, the mean urea clearances (Kt/V) and urea reduction ratio (URR) between the AVF- and the CVC-group were similar (P>0.05). The mean LVF values between the two groups were also similar before the establishment of vascular access (P>0.05), but the mean values of left ventricular end diastolic diameter (LVEDd), interventricular septal thickness (IVSTd), and left ventricular posterior wall thickness (LVPWT) in the AVF-group were higher than those in the CVC-group one year later, and mean early (E) and late (A) diastolic mitral velocities, E/A, and ejection fraction (EF) were lower than those in the CVC-group (P<0.05). The incidence of left ventricular hypertrophy and systolic dysfunction in the AVF-group was higher than that in the CVC-group (P<0.05). The hospitalization rate of AVF-group (23.02%) was lower than that of the CVC-group (49.61%) (P<0.05). Conclusion: Both AVF and CVC can achieve appropriate dialysis effects in MHD patients. AVF has a negative impact on cardiac function while CVC has a high hospitalization rate.

A Novel Surgical Approach for Rhinophyma: Experience From a Cohort of Thirty Patients.

BACKGROUND: Rhinophyma is the severe rosacea whit hypertrophy of sebaceous glands in nasal tissue, which severely influences the patient's appearance. Surgical therapy is the best method for treating moderate-to-severe rhinophyma. In this study, we used a new ameliorated scarification for 30 patients with moderate-to-severe rhinophyma. OBJECTIVE: To observe the effect of five-blades scratcher surgery on moderate-to severe rhinophyma between 2016 and 2019 in our center. MATERIALS AND METHODS: A total of 30 patients were treated with five-blades scratcher under tumescent anesthesia. Outcomes were determined by a patient questionnaire. RESULTS: Of 30 patients, all of them answered the questionnaire and were included in this study with a follow-up time of 12 months. Cosmetic results were evaluated as very good or good in 90% of patients. The majority of patients (87%) were very satisfied or satisfied with the postoperative result. Surgical treatment of rhinophyma improved patients' quality of life in 67% of patients. Recurrence of rhinophyma was detected in 7% of patients. In all, 100% of the patients stated that they would recommend this treatment to others. CONCLUSIONS: Five-blades scratcher is an effective therapy for rhinophyma with excellent outcome.

Design of Medical Image Detail Enhancement Algorithm for Ankle Joint Talar Osteochondral Injury.

Medical imaging modalities, such as magnetic resonance imaging (MRI) and computerized tomography (CT), have allowed medical researchers and clinicians to examine the structural and functional features of the human body, thereby assisting the clinical diagnosis. However, due to the highly controlled imaging environment, the imaging process often creates noise, which seriously affects the analysis of the medical images. In this study, a medical imaging enhancement algorithm is presented for ankle joint talar osteochondral injury. The gradient operator is used to transform the image into the gradient domain, and fuzzy entropy is employed to replace the gradient to determine the diffusion coefficient of the gradient field. The differential operator is used to discretize the image, and a partial differential enhancement model is constructed to achieve image detail enhancement. Three objective evaluation indexes, namely, signal-to-noise ratio (SNR), information entropy (IE), and edge protection index (EPI), were employed to evaluate the image enhancement capability of the proposed algorithm. Experimental results show that the algorithm can better suppress noise while enhancing image details. Compared with the original image, the histogram of the transformed image is more uniform and flat and the gray level is clearer.

A Surgical Management for Severe Rhinophyma With Five-Blade Scratcher.

ABSTRACT: Rhinophyma, the final stage of acne rosacea, severely influences the patient's appearance and can only be treated by surgical methods. This case reports a simple, safe, effective, and economical surgical method-five-blade scratcher. After the surgical treatment, the overall nasal contour of the patient, a male with severe rosacea, was restored without scar formation. Thus, this surgical method reported in this case is feasible and easy to operate, and worthy of clinical promotion.

TVT-O vs TVT-S for female stress urinary incontinence: A systematic review and meta-analysis.

BACKGROUND: Tension-free vaginal tape obturator (TVT-O) and tension-free vaginal tape secur (TVT-S) are common surgeries for the treatment of stress urinary incontinence (SUI), several randomised controlled trials (RCTs) have compared the effects of TVT-O and TVT-S, yet the results remained inconsistent. Therefore, we attempted to conduct this systematic review and meta-analysis to analyse the role of TVT-O and TVT-S in patients with SUI. METHODS: We searched PubMed databases from inception date to Jan 15, 2020 for RCTs that compared TVT-O and TVT-S in SUI patients. Two authors independently screened and extracted data from the published articles. Summary odd ratios (OR) or mean differences (MD) with 95% confidence intervals (95% CI) were calculated for each outcome by fixed- or random-effects model. RESULTS: Seven RCTs with a total of 755 patients were identified, with 373 patients for TVT-O and 382 patients for TVT-S. TVT-O preceded TVT-S in the objective cure at 12 months (OR = 1.72, 95% CI 1.21-2.45), subjective cure (OR = 1.98, 95% CI 1.08-3.62); but TVT-S have more advantage in the incidence of postoperative thigh pain (OR = 18.94, 95% CI 7.01-51.15); no significant differences on the duration of operative procedure (OR = -1.09, 95% CI -2.37-0.18), urinary retention (OR = 0.77, 95% CI 0.36-1.62) and urinary infection (OR = 1.80, 95% CI 0.63-5.13) were found. CONCLUSIONS: TVT-O should be preferred for patients with SUI even though with higher risks of postoperative thigh pain when compared with TVT-S, more related studies are needed to identify the role of TVT-O and TVT-S for the treatment of SUI.

Conditioned Medium Enhances Osteogenic Differentiation of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells.

Background: Recent studies have shown that induced pluripotent stem cells (iPSCs) could be differentiated into mesenchymal stem cells (MSCs) with notable advantages over iPSCs per se. In order to promote the application of iPSC-MSCs for osteoregenerative medicine, the present study aimed to assess the ability of murine iPSC-MSCs to differentiate into osteoblast phenotype. Methods: Osteogenic differentiation medium, blending mouse osteoblast-conditioned medium (CM) with basic medium (BM) at ratio 3:7, 5:5 and 7:3, were administered to iPSC-MSCs, respectively. After 14 days, differentiation was evaluated by lineage-specific morphology, histological stain, quantitative reverse transcription-polymerase chain reaction and immunostaining. Results: The osteogenesis-related genes, alp, runx2, col1 and ocn expressions suggest that culture medium consisting of CM:BM at the ratio of 3:7 enhanced the osteogenic differentiation more than other concentrations that were tested. In addition, the alkaline phosphatase activity and osteogenic marker Runx2 expression demonstrate that the combination of CM and BM significantly enhanced the osteogenic differentiation of iPSC-MSCs. Conclusion: In summary, this study has shown that osteoblast-derived CM can dramatically enhance osteogenic differentiation of iPSC-MSCs toward osteoblasts. Results from this work will contribute to optimize the osteogenic induction conditions of iPSC-MSCs and will assist in the potential application of iPSC-MSCs for bone tissue engineering.

Treatment with Radix Euphorbiae Ebracteolatae Significantly Decreases the Expression of E6 and L1, and Increases the Expression of p53 and Rb in HPV18-infected Human Foreskin Keratinocytes.

BACKGROUND: Radix Euphorbiae Ebracteolatae (REE) was recently reported to be significantly superior to vitamin A acid ointment in treating multiple plantar warts. However, the effects of REE on HPV18 remain unclear. Therefore, the current study aimed to investigate the effects of REE on the proliferation of HPV18, and explore possible molecular mechanisms underlying the effects. METHODS: HFK and HFK-HPV18 were treated with water-extracted single or compound REE, ethanol-extracted single or compound REE, TNF-α and IFN for 3 days, respectively. In addition, the organotypic rafts containing HFK-HPV18 and HFK were treated with REE, IFN and TNF-α for 7 days, respectively. Cell proliferation rates were measured with Brdu. mRNA expression of E6, L1, p53 and Rb was detected by qPCR. Protein expression of p53, Rb and L1 was detected by Western blot. RESULTS: Compared to HFK group, HFK-HPV18 group had significantly higher expression of E6 and L1. Compared to the control group, HFK-HPV18 treated with REE, TNF-α and IFN displayed significantly lower proliferation rates. The mRNA expression of E6 was markedly lower, and mRNA expression of p53 and Rb was significantly higher after treatment of REE in HFK-HPV18 or in organotypic rafts containing HFK-HPV18. Treatment with REE markedly increased the protein expression of p53 and Rb, and decreased the protein expression of L1 in HFK-HPV18 or in organotypic rafts containing HFK-HPV18. Among all formula of REE, the inhibition of proliferation rates and expression of E6 and L1, and the increase in expression of p53 and Rb in HFK-HPV18 was highest in ethanol-extracted compound REE group. CONCLUSIONS: The proliferation rates are significantly lower in HFK-HPV18 treated with REE. The expression of E6 and L1 is markedly lower, and expression of p53 and Rb is significantly higher after REE treatment in HFK-HPV18 or organotypic rafts containing HFK-HPV18. Among all formula of REE, ethanol-extracted compound REE displays the highest protection against HPV18.

Dynamic Balance Measurement and Quantitative Assessment Using Wearable Plantar-Pressure Insoles in a Pose-Sensed Virtual Environment.

The center of plantar pressure (COP) reflects the dynamic balance of subjects to a certain extent. In this study, wearable pressure insoles are designed, body pose measure is detected by the Kinect sensor, and a balance evaluation system is formulated. With the designed games for the interactive actions, the Kinect sensor reads the skeletal poses to judge whether the desired action is performed, and the pressure insoles simultaneously collect the plantar pressure data. The COP displacement and its speed are calculated to determine the body sway and the ability of balance control. Significant differences in the dispersion of the COP distribution of the 12 subjects have been obtained, indicating different balancing abilities of the examined subjects. A novel assessment process is also proposed in the paper, in which a correlation analysis is made between the de facto sit-to-stand (STS) test and the proposed method; the Pearson and Spearman correlations are also conducted, which reveal a significant positive correlation. Finally, four undergraduate volunteers with a right leg sports injury participate in the experiments. The experimental results show that the normal side and abnormal side have significantly different characters, suggesting that our method is effective and robust for balance measurements.

Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt.

Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the herbal medicine Radix Sophorae flavescentis, is used to treat allergic skin diseases in China. The non-cytotoxic concentrations of OMT in HaCaT cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Tumor necrosis factor (TNF)-α and IFN-γ were used to stimulate HaCaT cells, and OMT was added to this system with tacrolimus (FK506) as a positive control. The mRNAs of cytokines, MDC, ICAM-1, IL-12p35, IL-12p40, and IFN-γ receptor (IFN-γR)α were detected by RT-PCR. Western blot analyses were performed to assess activation of the MAPK (p38, Jun N-terminal kinase, and extracellular signal-regulated kinase) and Akt signaling pathways. OMT increased the mRNA levels of the IL-12 and IFN-γRα, reduced the mRNA levels of ICAM-1, MDC, and SOCS1. But FK506 increased the mRNA levels of IL12 and inhibited the expression of ICAM-1 mRNAs and had no effects on the IFN-γRα, MDC, and SOCS1 mRNA in HaCaT cells stimulated with TNF-α and IFN-γ. Thus, the mechanisms through which OMT and FK506 ameliorate allergic skin diseases differ.

Efficacy of topical administration of Radix Euphorbiae Ebracteolatae on multiple plantar warts: A parallel randomized trial.

OBJECTIVE: To investigate the clinical efficacy of Radix Euphorbiae Ebracteolatae in treating multiple plantar warts. METHODS: Twenty-eight patients with multiple plantar warts on both left and right feet were recruited. Warts on the left feet (treatment group) of all patients were externally treated with moderate ethanol extract of Radix Euphorbiae Ebracteolatae which was made of 30 g Radix Euphorbiae Ebracteolatae putting into 100 mL of medical ethanol (75%). For the control group, moderate dose of 0.1% vitamin A acid ointment was externally applied onto the right-foot warts. The topical application of each treatment was conducted 3 times a day for both groups. After 4 and 8 weeks, the efficacy and side effects including skin erythema and blister were evaluated and observed. RESULTS: Compared with the pre-treatment, warts size of the control group was reduced after 8-week treatment (P<0.05). After 4 and 8 weeks, the average wart size in the treatment group was both significantly reduced respectively (P<0.01). There were significant differences in warts size and total effective rate between the two groups after 4-week treatment respectively (P<0.05 or P<0.01). More significant differences in wart size and total effective rate were observed after 8-week treatment (P<0.05 or P<0.01). The percentage reduction in wart size was significantly different between the two groups after 4 and 8-week treatment (P<0.01). CONCLUSION: Radix Euphorbiae Ebracteolatae was significantly superior to vitamin A acid ointment in treating multiple plantar warts.

Evaluation of Anti-Inflammatory Activities of Qingre-Qushi Recipe (QRQS) against Atopic Dermatitis: Potential Mechanism of Inhibition of IL-33/ST2 Signal Transduction.

To evaluate the anti-inflammatory activities of QRQS against AD and the inhibitory molecular mechanisms of IL-33/ST2 signal transduction, BALB/c mice were divided into six groups (normal control, OVA control, low-dose of QRQS, middle-dose of QRQS, high-dose of QRQS, and cetirizine) and epicutaneously exposed to ovalbumin or PBS for 3 weeks and treated with QRQS for 2 weeks. Skin biopsies and blood samples were obtained for histological study, antibody analysis, and RNA isolation. HaCaT cells, stimulated by TNF-α and IFN-γ, were treated with QRQS to evaluate mRNA and protein expression by RT-PCR and ELISA. QRQS decreased both epidermal and dermal thickness, alleviated dermatitis, and reduced IL-33 and ST2 positive cell numbers. The concentration of specific IgE, IgG, IgG1, and IgG2a antibodies in serum and the expression of IL-33, ST2, IL-1RAcP, IL-4, and IL-13 mRNA in the skin were suppressed. No significant difference exists in TNF-α or IFN-γ. QRQS decreased IL-33 mRNA and protein secretion in HaCaT cells exposed to TNF-α and IFN-γ in a time- and concentration-dependent manner. QRQS regulates related molecule expression of ovalbumin-induced dermatitis involved in the IL-33/ST2 signaling axis in the treatment of acute AD.

Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway.

The histamine receptor antagonists in the treatment of allergic disease have limitations. The treatments of Chinese herbs have some curative effects on allergic skin lesions. Present research indicates that the mitogen-activated protein kinase (MAPK) signaling pathway might be equally important in allergic reactions. It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms, and some herbs can inhibit the MAPK pathway, which yields anti-allergy effects. Chinese medicines (CMs) have immense potential in the development of treatments for allergic disease.

Salvianolic acid B promotes bone formation by increasing activity of alkaline phosphatase in a rat tibia fracture model: a pilot study.

BACKGROUND: Radix Salviae miltiorrhizae is a herb frequently used within traditional Chinese medicine for the treatment of cardiovascular- and trauma-related diseases. Danshen is the dried root of Salviae miltiorrhizae, from which the polyphenolic compound Salvianolic acid B (Sal B) can be obtained. Sal B is a key component of Danshen. The aim of this study was to determine the effect of Sal B on the healing of long bones following trauma in a rat tibia fracture model. METHODS: Tibia fractures were created in 20 male Sprague Dawley rats. The animals were divided into two groups: (1) experimental group (n = 10); and (2) control group (n = 10). Rats in the experimental group were intraperitoneally administered with Sal B (40 mg/kg/d) for 3 weeks, while rats in the control group received an identical volume of physiological saline solution, administered in the same way. X-ray photographs were taken of all animals at the time points. Rats were euthanized at weeks 1, 3, 8 and 12 post-fracture. Fracture calluses were measured and callus sections were obtained and stained using hematoxylin and eosin (HE) and the calcium cobalt method. HE stained sections were observed and evaluated according to different grades of bone remodeling. Sections stained using the calcium cobalt method were analyzed with an imagine analysis system. RESULTS: Data showed that callus growth was significantly greater in the experimental group compared with the control group (P < 0.05). Furthermore, histological scores in the Sal B-treated group were statistically higher than in the saline treated group at weeks 1, 3 and 8 post-fracture (P < 0.05). Alkaline phosphatase (ALP) activity was enhanced in the experimental group at weeks 1 and 3 post-fracture (P < 0.05). CONCLUSIONS: Our results suggest that Sal B may accelerate early-stage fracture healing. Increased activity of ALP may be one factor which promotes the healing process. This pilot study provides brief insight into the effect of Sal B in fracture healing. These findings will contribute to the development of more and enhanced treatment options for trauma fracture patients.

Exploring the host parasitism of the migratory plant-parasitic nematode Ditylenchus destuctor by expressed sequence tags analysis.

The potato rot nematode, Ditylenchus destructor, is a very destructive nematode pest on many agriculturally important crops worldwide, but the molecular characterization of its parasitism of plant has been limited. The effectors involved in nematode parasitism of plant for several sedentary endo-parasitic nematodes such as Heterodera glycines, Globodera rostochiensis and Meloidogyne incognita have been identified and extensively studied over the past two decades. Ditylenchus destructor, as a migratory plant parasitic nematode, has different feeding behavior, life cycle and host response. Comparing the transcriptome and parasitome among different types of plant-parasitic nematodes is the way to understand more fully the parasitic mechanism of plant nematodes. We undertook the approach of sequencing expressed sequence tags (ESTs) derived from a mixed stage cDNA library of D. destructor. This is the first study of D. destructor ESTs. A total of 9800 ESTs were grouped into 5008 clusters including 3606 singletons and 1402 multi-member contigs, representing a catalog of D. destructor genes. Implementing a bioinformatics' workflow, we found 1391 clusters have no match in the available gene database; 31 clusters only have similarities to genes identified from D. africanus, the most closely related species to D. destructor; 1991 clusters were annotated using Gene Ontology (GO); 1550 clusters were assigned enzyme commission (EC) numbers; and 1211 clusters were mapped to 181 KEGG biochemical pathways. 22 ESTs had similarities to reported nematode effectors. Interestedly, most of the effectors identified in this study are involved in host cell wall degradation or modification, such as 1,4-beta-glucanse, 1,3-beta-glucanse, pectate lyase, chitinases and expansin, or host defense suppression such as calreticulin, annexin and venom allergen-like protein. This result implies that the migratory plant-parasitic nematode D. destructor secrets similar effectors to those of sedentary plant nematodes. Finally we further characterized the two D. destructor expansin proteins.

Sensitive and Direct Detection of Heterodera filipjevi in Soil and Wheat Roots by Species-Specific SCAR-PCR Assays.

Cereal cyst nematodes are the most important plant-parasitic nematodes on cereal crops in wheat producing areas of the world. Heterodera filipjevi was first reported in China in 2010. In this study, species-specific sequence characterized amplified region-polymerase chain reaction (SCAR-PCR) assays for detection and identification of H. filipjevi from infected wheat roots and soil were developed. The species-specific primers were designed according to the randomly amplified polymorphic DNA (RAPD) markers amplified with random primer OPK16. A 646-bp specific fragment of sequence was generated, which characterized amplified regions in H. filipjevi. The detection limitation of the PCR assay was as low as 0.125 µl second-stage juvenile (J2) lysate, 3.9 × 10-3 µl adult female lysate, and 10-3 µl cyst lysate. The method was able to detect the various stages (J2, J3, J4, and female) of H. filipjevi, and a single of nematode in 0.5 g of soil. H. filipjevi was detected by the method in two of six field samples, and one of those samples contained a mixed population of H. filipjevi and H. avenae. This study is the first to provide a definitive diagnostic assay for H. filipjevi in wheat roots and soil.