Dysregulated tryptophan metabolism and AhR pathway contributed to CXCL10 upregulation in stable non-segmental vitiligo.

BACKGROUND: Tryptophan metabolism dysregulation has been observed in vitiligo. However, drawing a mechanistic linkage between this metabolic disturbance and vitiligo pathogenesis remains challenging. OBJECTIVE: Aim to reveal the characterization of tryptophan metabolism in vitiligo and investigate the role of tryptophan metabolites in vitiligo pathophysiology. METHODS: LC-MS/MS, dual-luciferase reporter assay, ELISA, qRT-PCR, small interfering RNA, western blotting, and immunohistochemistry were employed. RESULTS: Kynurenine pathway activation and KYAT enzyme-associated deviation to kynurenic acid (KYNA) in the plasma of stable non-segmental vitiligo were determined. Using a public microarray dataset, we next validated the activation of kynurenine pathway was related with inflammatory-related genes expression in skin of vitiligo patients. Furthermore, we found that KYNA induced CXCL10 upregulation in keratinocytes via AhR activation. Moreover, the total activity of AhR agonist was increased while the AhR concentration per se was decreased in the plasma of vitiligo patients. Finally, higher KYAT, CXCL10, CYP1A1 and lower AhR expression in vitiligo lesional skin were observed by immunohistochemistry staining. CONCLUSION: This study depicts the metabolic and genetic characterizations of tryptophan metabolism in vitiligo and proposes that KYNA, a tryptophan-derived AhR ligand, can enhance CXCL10 expression in keratinocytes.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC.

Ultrasound elastography predicts anticoagulation in lower extremity deep vein thrombosis.

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

The efficiency and safety of low-dosage isotretinoin therapy for Chinese acne vulgaris patients.

BACKGROUND: Acne vulgaris is one of the most common skin conditions in dermatology clinics. Accumulating evidence has implicated oral low-dosage isotretinoin was an effective treatment for acne with fewer side effects. Currently, the data on low-dosage isotretinoin use in Chinese is limited. AIMS: To investigate the efficiency and safety of low-dosage isotretinoin therapy for Chinese acne patients. METHODS: Three hundred and eighty-eight patients treated with low-dosage isotretinoin (0.2-0.4 mg/kg/d) and who completed the course (120 mg/kg) were enrolled. Medical information on the severity, duration, adverse effects, and outcome of acne was reviewed. RESULTS: The majority (90.2%, n = 350) of patients achieved complete remission, and on average, patients received 13.5 months of treatment. The time between isotretinoin start and the clear date between the mild and moderate groups was not significantly different (74 ± 24 vs. 84 ± 24 days). However, it took longer to resolve for the severe acne group (112 ± 25 days). Follow-up 1 year after completion of the isotretinoin course, 37/350 (10.6%) patients relapsed, but there was no difference in the severity of acne. There were 133 (34.3%), 40 (10.3%), and 14 (2.6%) patients who developed hypercholesterolemia, hypertriglyceridemia, and high LDL, respectively. Thirty-two (8.2%) and 28 patients (7.2%) had elevated serum levels of alanine and aspartate aminotransferases. No values above grade 2 were detected. CONCLUSIONS: This study reaffirms the efficacy and safety of low-dosage oral isotretinoin in Chinese patients with acne vulgaris. Lab investigation could be performed after 2 months of therapy in healthy patients with normal baseline liver function and lipid panel tests.

[Bisulfite Promoted Minute Fe2+-Activated Peroxydisulfate for Paracetamol Degradation].

Fe2+ has been commonly selected to activate peroxydisulfate(PDS) for sulfate radical(SO4-·) generation because of its eco-friendly, cost-effective, and high activity characteristics. However, Fe2+ can be rapidly oxidized to Fe3+ in the reaction, leading to poor utilization of iron for PDS activation. Further, a fairly high concentration of Fe2+ is generally required and may cause iron sludge production and secondary pollution. In this study, a minute Fe2+-activated PDS system induced by bisulfite(BS) was used to degrade paracetamol(APAP) in water. The results showed that the Fe2+-PDS system could be enhanced by the circulation of Fe2+-Fe3+ with the injection of BS and by keeping Fe2+ at a high concentration. Under the optimal conditions(PDS=0.6 mol·L-1; BS=0.4 mol·L-1; Fe2+=10 µmol·L-1; pH=4), 100% APAP(4 µmol·L-1) was removed within 180 s. The degradation rate of APAP increased with the increase in BS(0-0.6 mmol·L-1) and PDS(0.2-1.5 mmol·L-1) concentration, and a modest Fe2+ concentration could accelerate APAP removal. Co-existing substances inhibited the APAP removal and followed the order of HCO3->HPO42->Cl->NO3->humic acid(HA). Based on the quenching experiments and electron paramagnetic resonance spectroscopy test, SO4-· was shown to be the primary reactive species for APAP decomposition in the BS-Fe2+-PDS process. Three-dimensional fluorescence spectroscopy revealed that APAP intermediates had fluorescence characteristics. Moreover, five intermediates were identified, and the probable APAP degradation pathways were proposed. The removal efficiencies of APAP were lower in real waters than that in ultrapure water. Nevertheless, the removal effect was greatly improved after a prolonged reaction time. All results indicated that the BS-Fe2+-PDS system could be a promising method for organic pollutant treatment.

COVID-19 risk perception and negative emotional symptoms: Mediating role of self-control and moderating role of life history strategy.

The coronavirus disease 2019 (COVID-19) has emerged as a significant public health crisis, posing threats to physical health and mental well-being. This study, grounded in the Risk-Resilience Model, sought to elucidate how COVID-19 risk perception impacts negative emotional symptoms. Specifically, we examined the mediating role of self-control and the moderating role of life history strategies. We conducted a two-wave longitudinal survey in October 2020 (N = 334) and November 2020 (N = 249), targeting residents across 14 provinces (24 cities) in China. After controlling for sex and age, the results supported the moderated mediation model, illustrating that (1) self-control mediated the relationship between COVID-19 risk perception and negative emotional symptoms, (2) life history strategy moderated the first segment of the mediation process, and (3) life history strategies also moderated the mediating effect of self-control on the link between COVID-19 risk perception and negative emotional symptoms. Furthermore, compared to a fast life history strategy, a slow life history strategy mitigated the effect of COVID-19 risk perception on self-control, thereby reducing negative emotional symptoms. This study sheds light on how COVID-19 risk perception affects negative emotional symptoms and identifies potential targets (i.e., self-control and life history strategy) for addressing emotional distress during pandemics.

TMT-Based Quantitative Proteomic and Physiological Analyses on Serums of Chinese Patients with Active Vitiligo.

Purpose: Vitiligo is an acquired depigmented skin disorder. Though genetic background, autoimmune dysregulation, and oxidative stress were reported involved in the development of vitiligo, the exact pathogenesis remains largely unknown. This study aimed to investigate potential functional proteins, pathways, and serum biomarkers involved in active vitiligo. Patients and Methods: Tandem Mass Tags (TMT) method was used to determine differentially expressed proteins (DEPs) in serum samples between 11 active vitiligo patients and 7 healthy controls of Chinese Han population. Results: A total of 31 DEPs were identified (P < 0.05, fold change >1.2), with 21 proteins upregulated and 10 proteins downregulated in the vitiligo group. DEPs were enriched in GO terms such as "extracellular exosome" and "immunoglobulin receptor binding", as well as KEGG pathways including "cysteine and methionine metabolism" and other immune-related pathways. Furthermore, ALDH1A1 and EEF1G achieved areas under receiver-operating characteristic (ROC) curve of 0.9221 and 0.8571, respectively. The expression levels of these 2 proteins were validated in another active vitiligo patient group. Conclusion: Our research provided novel insight into serum proteomic profile for vitiligo patients, detecting ALDH1A1 and EEF1G as potential biomarkers for active vitiligo and therapeutic intervention. Our work also detected several DEPs and associated pathways in the serum of active vitiligo patients, reinforcing the roles of retinoic acid and exosome processes in vitiligo pathogenesis.

Roflumilast enhances the melanogenesis and attenuates oxidative stress-triggered damage in melanocytes.

BACKGROUND: The management of vitiligo is challenging due to limited treatment options, and therapeutic strategy varies according to the active or stable stage of vitiligo. PDE4 inhibitor has been used to treat various skin diseases, but the efficacy in vitiligo treatment is mixed. OBJECTIVE: In this study, we aimed to investigate whether roflumilast, a PDE4 inhibitor, induces melanogenesis and attenuates oxidative stress-triggered damage in melanocytes, and if so, what is the mechanism. METHODS: Melanin content assay, qRT-PCR, western blotting, ELISA, immunofluorescence assays, immunohistochemistry, small interfering RNA, flow cytometry, and transmission electron microscopy were employed. RESULTS: Our results demonstrated that roflumilast alone only slightly increased melanogenesis, however, the combination of roflumilast and forskolin could boost cAMP levels, hence promoting melanogenesis more significantly. Moreover, roflumilast attenuated H2O2-induced apoptosis and mitochondrial morphological changes in melanocytes by reducing ROS levels. Furthermore, roflumilast activated AhR/Nrf2 pathway via cAMP whereas AhR silencing blocked roflumilast-induced Nrf2 nuclear translocation and reversed the inhibitory effect of roflumilast on H2O2-induced ROS production. Finally, we observed that the lesional skin of active vitiligo patients exhibited higher PDE4 expression levels. CONCLUSION: roflumilast enhances the melanogenesis effect of forskolin and protects melanocytes from H2O2-induced apoptosis by cAMP/AhR/Nrf2-activated ROS inhibition, highlighting its therapeutic potential in vitiligo treatment.

Atrophic dermatofibrosarcoma protuberans: Two case reports and literature review.

Dermatofibrosarcoma protuberans is a rare, locally aggressive, slowly growing cutaneous fibroblastic sarcoma with a high recurrence rate and low metastatic potential. Atrophic dermatofibrosarcoma protuberans is a rare variant usually presents as atrophic plaques, easily neglected and misdiagnosed as benign lesions by patients and dermatologists. Here we report two cases of atrophic dermatofibrosarcoma protuberans, one of which was accompanied by pigment, and review other cases have been reported in the literature. Understanding the most up-to-date literature and early identification of these dermatofibrosarcoma protuberans variants can help clinicians avoid delayed diagnosis and improve prognosis.

The Relationship Between Meaning in Life and Health Behaviors in Adults Aged 55 Years and Over During the COVID-19 Pandemic: the Mediating Role of Risk Perception and the Moderating Role of Powerful Others Health Locus of Control.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted many people's meaning in life and health behaviors. This study aimed to verify the relationship among meaning in life (MIL), epidemic risk perception, health locus of control (HLC), and preventive health behaviors among older adults after the COVID-19 outbreak was declared a pandemic. METHOD: In this longitudinal study, 164 participants aged 55 years and above completed the following measures at time 1 (February 19, 2021) and one month later at time 2 (March 19, 2021): Meaning in Life in the Epidemic Questionnaire, Epidemic Risk Perception Questionnaire, Multidimensional Health Locus of Control Scale, and Health Behaviors Before and After the Epidemic Survey. Hayes' SPSS Process Macro was used to analyze the mediating effect of epidemic risk perception (model 4) and the moderating role of powerful others HLC in the mediation model (model 14). RESULTS: The results showed that after controlling for gender, age, education level, and health behaviors at the baseline, risk perception had a significant mediating effect on the relationship between MIL and preventive health behaviors (ß = .02, SE = .01, 95% CI [.00, .04]). In addition, powerful others HLC had a moderating effect on the second half of the mediating effect (ß = .02, p = .02, 95% CI [.00, .03]). Specifically, compared to the older adults with low powerful others HLC, the risk perception of older adults with high powerful others HLC increased preventive health behaviors. CONCLUSION: Practitioners should adequately cultivate older adults' risk awareness and reinforce the importance of advice from doctors and professionals, thereby effectively enhancing the preventive health behaviors of older adults in China during the COVID-19 pandemic.

Nodular and diffuse spindle cell infiltration in keloidal scleroderma: a case report.

Keloidal scleroderma is a variant of scleroderma that presents as firm keloidal nodules or plaques. Due to the similarity in morphology and pathology, it is often distinguished from a hypertrophic scar or keloid. We report a case of keloidal scleroderma with rare nodular and diffuse spindle cell infiltration in histopathology. Recognition of this unusual histopathological feature may help clinicians improve their knowledge and avoid misdiagnosis.

Eyebrow tattoo-associated sarcoidosis: A case report.

Cutaneous sarcoidosis can manifest after doing a permanent makeup (PMU), such as tattooed eyebrows. A 41-year-old Chinese woman, with a tattoo in the eyebrows, developed yellow-brown plaques in her eyebrows for several months. A dermatopathological examination revealed non-caseating granulomas consistent with cutaneous sarcoidosis. For months, topical corticosteroids were applied, which showed little effect. Furthermore, a physical evaluation of the patient revealed no apparent involvement of other body organs except bilateral hilar lymphadenopathy with few diffuse reticulonodular opacities. On the basis of fully informed consent, the patient agreed to a 6-month initial follow-up to avoid unnecessary PMU.

Noncoding RNAs involved in DNA methylation and histone methylation, and acetylation in diabetic vascular complications.

Diabetes is a metabolic disorder and its incidence is still increasing. Diabetic vascular complications cause major diabetic mobility and include accelerated atherosclerosis, nephropathy, retinopathy, and neuropathy. Hyperglycemia contributes to the pathogenesis of diabetic vascular complications via numerous mechanisms including the induction of oxidative stress, inflammation, metabolic alterations, and abnormal proliferation of EC and angiogenesis. In the past decade, epigenetic modifications have attracted more attention as they participate in the progression of diabetic vascular complications despite controlled glucose levels and regulate gene expression without altering the genomic sequence. DNA methylation and histone methylation, and acetylation are vital epigenetic modifications and their underlying mechanisms in diabetic vascular complication are still urgently needed to be investigated. Non-coding RNAs (nc RNAs) such as micro RNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circ RNAs) were found to exert transcriptional regulation in diabetic vascular complication. Although nc RNAs are not considered as epigenetic components, they are involved in epigenetic modifications. In this review, we summarized the investigations of non-coding RNAs involved in DNA methylation and histone methylation and acetylation. Their cross-talks might offer novel insights into the pathology of diabetic vascular complications.

Low-viscosity sodium alginate combined with TiO2 nanoparticles for improving neuroblastoma treatment.

Titanium dioxide (TiO2) nanoparticles have been explored to prevent various cancer developments but it may cause oxidation, inflammation and high cytotoxicity. Alginate has nontoxic, anti-inflammatory, and antioxidant effects. We aimed to explore the effects of alginate-TiO2 temozolomide (TMZ) nanoparticles on neuroblastoma. A neuroblastoma model was established with neuroblastoma cells and alginate-TiO2 TMZ nanoparticles were made by spraying low-viscosity sodium alginate (250-360 kDa). The morphology of nanoparticles was observed via scanning electron microscope (SEM). The crystallinity values were analyzed via X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopic study. Neuroblastoma mice were treated with saline solution, TMZ, TiO2-TMZ and alginate-TiO2-TMZ nanoparticles. Anti-oxidant, anti-inflammatory, and anti-tumor properties and the mouse survival rates were measured. The spectrometric profiles of alginate-TiO2 were consistent with those of TiO2 and alginate. Alginate-TiO2 TMZ nanoparticles had higher cytotoxicity toward neuroblastoma cells and less inhibitory activity toward normal neuronal cells. The combined nanoparticles increased antioxidant, anti-inflammatory and antitumor activities and prolonged the survival time of the neuroblastoma model (P < 0.05). On the other hand, Alginate-TiO2 TMZ nanoparticles reduced the levels of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). The combined nanoparticles improved neuroblastoma treatment by affecting NF-κB and MAPK signals.

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes.

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

Identification of a cryptic submicroscopic deletion using a combination of fluorescence in situ hybridization and array comparative genomic hybridization in a t(3;5)(q25;q35)-positive acute myeloid leukemia patient: A case report and review of the literature.

RATIONALE: The advent of high-resolution genome arrays including array comparative genomic hybridization (aCGH) has enabled the detection of cryptic submicroscopic deletions flanking translocation breakpoints in up to 20% of the apparently "balanced" structural chromosomal rearrangements in hematological disorders. However, reports of submicroscopic deletions flanking the breakpoints of t(3;5)(q25;q35) are rare and the clinical significance of submicroscopic deletions in t(3;5) has not been explicitly identified. PATIENT CONCERNS: We present a 47-year-old man with acute myeloid leukemia. G-banding analysis identified t(3;5)(q25;q35). DIAGNOSIS: Array CGH-based detection initially confirmed only the deletion of chromosome 3. Further characterization using fluorescence in situ hybridization identified a cryptic submicroscopic deletion including 5' MLF1-3' NPM1 flanking the breakpoint on the derivative chromosome 3. INTERVENTIONS: The patient started "7+3" induction chemotherapy with cytosine arabinoside and daunorubicin, and subsequently received 2 cycles of high-dose intermittent acronym of cytosine arabinoside or cytarabine. OUTCOMES: The patient did not undergo complete remission and died from an infection due to neutropenia. LESSONS: Haploinsufficiency of NPM1 or other deleted genes, including SSR3, may be responsible for the phenotype of t(3;5)(q25;q35)-positive myeloid neoplasms with submicroscopic deletions.

Pro-inflammatory role of cell-free mitochondrial DNA in cardiovascular diseases.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Inflammation contributes to the pathogenesis and progression of CVD. Circulating cell-free mitochondrial DNA (ccf-mtDNA) is that mtDNA fragments are released outside the cell and into the circulation by cell necrosis and secretion. The levels of ccf-mtDNA are increased in CVD and associated risk conditions, including hypercholesterolemia, diabetes mellitus, and arterial hypertension. MtDNA containing unmethylated CpG dinucleotides and can trigger inflammation that aggravates tissue injury by activating toll-like receptor 9, inflammasomes, and the stimulator of interferon genes pathway. Here, we review the expanding field of ccf-mtDNA-mediated inflammation and its role in the progression of CVD.