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1.
Clin Exp Dermatol ; 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38641554

RESUMO

BACKGROUND: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen's disease (BD). However, reported data on 5-aminolevulinic acid-mediated PDT (ALA-PDT) with red light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. METHODS: Medical records of BD patients who received ALA-PDT with red light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were performed to identify risk predictors. RESULTS: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first two years following ALA-PDT. CONCLUSION: ALA-PDT is an effective treatment for BD in the skin of color patients. Well-executed operation and effective pre-treatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, two years of follow-up is necessary following ALA-PDT.

2.
Heliyon ; 10(7): e28942, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601678

RESUMO

Ferroptosis is an iron-dependent programmed cell death modality, which has showed great potential in anticancer treatment. Photodynamic therapy (PDT) is widely used in clinic as an anticancer therapy. PDT combined with ferroptosis-promoting therapy has been found to be a promising strategy to improve anti-cancer therapy efficacy. Fenton reaction in ferroptosis can provide oxygen for PDT, and PDT can produce reactive oxygen species for Fenton reaction to enhance ferroptosis. In this review, we briefly present the importance of ferroptosis in anticancer treatment, mechanism of ferroptosis, researches on PDT induced ferroptosis, and the mechanism of the synergistic effect of PDT and ferroptosis on cancer killing.

3.
Nat Commun ; 15(1): 2552, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38514649

RESUMO

Sulfide electrolytes represent a crucial category of superionic conductors for all-solid-state lithium metal batteries. Among sulfide electrolytes, glassy sulfide is highly promising due to its long-range disorder and grain-boundary-free nature. However, the lack of comprehension regarding glass formation chemistry has hindered their progress. Herein, we propose interstitial volume as the decisive factor influencing halogen dopant solubility within a glass matrix. We engineer a Li3PS4-Li4SiS4 complex structure within the sulfide glassy network to facilitate the release of interstitial volume. Consequently, we increase the dissolution capacity of LiI to 40 mol% in 75Li2S-25P2S5 glass. The synthesized glass exhibits one of the highest ionic conductivities among reported glass sulfides. Furthermore, we develop a glassy/crystalline composite electrolyte to mitigate the shortcomings of argyrodite-type sulfides by utilizing our synthesized glass as the filler. The composite electrolytes effectively mitigate Li intrusion. This work unveils a protocol for the dissolution of halogen dopants in glass electrolytes.

4.
Inorg Chem ; 63(13): 5852-5864, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38507718

RESUMO

Four kinds of polyoxometalate (POM)-viologen compounds were synthesized by hydrothermal method, namely (1-cby)2·[H2(SiMo12O40)]·2H2O (1), (1-cby)2·[H2(SiW12O40)]·2H2O (2), (1-cby)2·(1,1'-bcby)2·{H4[Co4(H2O)2(PW9O34)2]}·12H2O (3), (1-cby)·(1,1'-bcby)·[H(α-PW11O39)CoII(1-cby)]·8H2O (4) (1-cby·Br = 1-Cyclopropylmethyl-[4,4']bipyridinyl-1-ium bromide, 1,1'-bcby·Br = 1,1'-Bis-cyclopropylmethyl-[4,4']bipyridinyl-1-ium bromide). These four POM-viologen compounds exhibit one-dimensional supramolecular network structures. Especially, compound 3 contains a rare sandwich POM subunit {Co4(H2O)2(PW9O34)2}10-. These four compounds can be used as color-changing materials, and they all exhibit noticeable color changes upon exposure to light, heat, and electricity. The discoloration mechanism involves viologen derivatives with electron-deficient properties accepting electrons from POM with electron-rich properties under external stimulation, leading to the formation of viologen free radicals. Among them, compounds 1 and 2 also have good properties for ink-free erasable printing, double anticounterfeiting, and ultraviolet detector because of their rapid color response to ultraviolet (UV) light. In addition, compounds 1-4 also show different color changes in the detection of volatile amines.

5.
J Evid Based Med ; 17(1): 207-223, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38530771

RESUMO

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.


Assuntos
Gastroenteropatias , Medicina Integrativa , Humanos , Medicina Tradicional Chinesa , Gastroenteropatias/prevenção & controle , Medicina Baseada em Evidências
6.
BMC Cancer ; 24(1): 342, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486189

RESUMO

BACKGROUND: Regular Low-Dose Computed Tomography (LDCT) for lung cancer high-risk population has been proved to improve health outcomes and relieve disease burden efficiently for both individual and society. With geographical impedance becoming the major barrier preventing patients from getting timely healthcare service, this study incorporated health seeking behavior in estimating spatial accessibility of relative scarce LDCT resource in China, thus to provide real-world evidence for future government investment and policy making. METHODS: Taking Sichuan Province in southwest China as the study area, a cross-sectional survey was first carried out to collect actual practice and preferences for seeking LDCT services. Using Computed Tomography (CT) registration data reported by owner institutions representing LDCT services capacity, and grided town-level high-risk population as demand, the Nearest Neighbor Method was then utilized to calculate spatial accessibility of LDCT services. RESULTS: A total of 2,529 valid questionnaires were collected, with only 34.72% of the high-risk populations (746 individuals) followed the recommended annual screening. Participants preferred to travel to municipal-level and above institutions within 60 min for LDCT services. Currently, every thousand high-risk populations own 0.0845 CT scanners in Sichuan Province, with 96.95% able to access LDCT within 60 min and over half within 15 min. Urban areas generally showed better accessibility than rural areas, and the more developed eastern regions were better than the western regions with ethnic minority clusters. CONCLUSIONS: Spatial access to LDCT services is generally convenient in Sichuan Province, but disparity exists between different regions and population groups. Improving LDCT capacity in county-level hospitals as well as promoting health education and policy guidance to the public can optimize efficiency of existing CT resources. Implementing mobile CT services and improving rural public transportation may alleviate emerging disparities in accessing early lung cancer detection.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Estudos Transversais , Detecção Precoce de Câncer/métodos , Etnicidade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Grupos Minoritários , Tomografia Computadorizada por Raios X/métodos , Análise Espacial , China/epidemiologia
7.
Small ; : e2400980, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38545991

RESUMO

Polyolefin separators are the most commonly used separators for lithium batteries; however, they tend to shrink when heated, and their Li+ transference number (t Li +) is low. Metal-organic frameworks (MOFs) are expected to solve the above problems due to their high thermal stability, abundant pore structure, and open metal sites. However, it is difficult to prepare high-porosity MOF-based membranes by conventional membrane preparation methods. In this study, a high-porosity free-standing MOF-based safety separator, denoted the BCM separator, is prepared through a nano-interfacial supramolecular adhesion strategy. The BCM separator has a large specific surface area (450.22 m2 g-1) and porosity (62.0%), a high electrolyte uptake (475 wt%), and can maintain its morphology at 200 °C. The ionic conductivity and t Li + of the BCM separator are 1.97 and 0.72 mS cm-1, respectively. Li//LiFePO4 cells with BCM separators have a capacity retention rate of 95.07% after 1100 cycles at 5  C, a stable high-temperature cycling performance of 300 cycles at 80 °C, and good capacity retention at -40 °C. Li//NCM811 cells with BCM separators exhibit significantly improved rate performance and cycling performance. Pouch cells with BCM separators can work at 120 °C and have good safety at high temperature.

9.
J Affect Disord ; 355: 487-494, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38548202

RESUMO

BACKGROUND: We aimed to prospectively examine the association of baseline allostatic load (AL) and longitudinal AL changes with incident cardiovascular disease (CVD) and all-cause mortality among middle-aged and elderly Chinese populations and evaluate the relative contributions of each physiological system of AL. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) among adults aged 45 years or older were analyzed. Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for the associations between baseline AL/longitudinal AL changes with incident CVD and all-cause mortality. RESULTS: Compared with adults with AL 0-1, HRs of those with baseline AL 2-3 and AL ≥ 4 were 1.24 (95 % CI: 1.06, 1.45) and 1.51 (95 % CI: 1.27, 1.80) for incident CVD, and 1.39 (95 % CI: 1.11, 1.75) and 2.02 (95 % CI: 1.60, 2.54) for all-cause mortality. Similar results were found when we treated baseline AL as a continuous variable. We also found per AL score increase during 4 years of follow-up was related to a 11 % (HR, 1.11; 95 % CI: 1.03, 1.20) and 21 % (HR, 1.21; 95 % CI: 1.10, 1.34) increase in incident CVD and all-cause mortality, respectively. LIMITATIONS: Self-reported physician-diagnosed CVD was used to assess the incident CVD. CONCLUSIONS: Both baseline AL and longitudinal increases in AL were positively associated with incident CVD and all-cause mortality in middle-aged and elderly adults. Individuals with high AL need to be dynamically monitored for CVD and pre-mature mortality prevention.


Assuntos
Alostase , Doenças Cardiovasculares , Idoso , Adulto , Pessoa de Meia-Idade , Humanos , Doenças Cardiovasculares/epidemiologia , Estudos Longitudinais , Estudos de Coortes , Fatores de Risco
10.
J Hazard Mater ; 469: 133914, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38430598

RESUMO

Persistent organic pollutants (POPs) sourced by the forest fire release are emerging as significant contributors. Despite their increasing importance, the impact of forest fires on POPs remains inadequately explored and an unclear understanding. Herein, the research, choosing four typical forest combustibles, focuses on the relationship between typical POPs and wildfire parameters by assessing the predominant compounds and their concentration in POPs emissions from such fuels through molecular-level analysis. Experiments reveal forest combustibles thermally degrade to release products, releasing a variety of products, including acids (>7.94 %), aldehydes (>2.32 %), ketones (>3.40 %), alcohols (>7.70 %), esters (>2.33 %), ethers (>4.44 %), hydrocarbons (>6.36 %), aromatic compounds (>21.40 %), and nitrogen-bearing compounds (>11.83 %); notably, aromatic compounds, containing substantial concentrations, are also recognized as POPs. By delving into the pyrolysis (20 °C·ms-1) and burning processes (25, 35 and 50 kW/m2) of forest combustibles, we can gain a comprehensive understanding of the origin of POPs in wildfires. Moreover, Pearson correlation analysis is employed to establish connections between emitting volatiles and forest fire risk, further unveiling a significant correlation between fire hazards of forest combustibles and the presence of aromatic compounds (Correlation over 0.8). These findings are crucial for comprehending the POPs in forests and evaluating forest fire hazards at the molecular level.

11.
Photodiagnosis Photodyn Ther ; 45: 103973, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38316341

RESUMO

BACKGROUND: Seborrhea poses a common cosmetic concern in adolescents and young adults, often accompanied by enlarged pores, and contributing to various skin conditions, including acne vulgaris and seborrheic dermatitis. At present, there is a lack of effective treatment for this problem, and the potential of photodynamic therapy (PDT) in reducing sebum remains inconclusive. OBJECTIVE: This exploratory, prospective, single-center, double-blinded, randomized split-face controlled trial aimed to compare the efficacy and safety of intense pulsed light-photodynamic therapy (IPL-PDT) versus IPL therapy for seborrhea. METHODS: Participants with seborrhea underwent 3 times of IPL treatment (590 nm, 15-17 J/cm2 based on patient's tolerance) for one hemifacial part and IPL-PDT treatment for the other. Follow-up assessment was conducted up to 8 weeks after the final treatment. RESULTS: Compared with single IPL treatment, IPL-PDT can significantly inhibit sebum secretion and decrease pore size. PDT group exhibited no additional damage to the skin barrier, with even lower transepidermal water loss (TEWL). Additionally, the PDT group showed superior improvement in scores of porphyrins, red areas, and ultraviolet (UV) spots. Both groups experienced only mild topical adverse effects, well tolerated by the participants. CONCLUSION: IPL-PDT is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function.


Assuntos
Acne Vulgar , Dermatite Seborreica , Fotoquimioterapia , Adolescente , Adulto Jovem , Humanos , Dermatite Seborreica/tratamento farmacológico , Estudos Prospectivos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Acne Vulgar/tratamento farmacológico
12.
BMC Public Health ; 24(1): 423, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336709

RESUMO

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.


Assuntos
Acesso aos Serviços de Saúde , Hospitais , Humanos , Teorema de Bayes , Fatores Socioeconômicos , China
13.
Am J Hematol ; 99(4): 774-779, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38343062

RESUMO

Jaktinib, a novel JAK and ACVR1 inhibitor, has exhibited promising results in treating patients with myelofibrosis (MF). ZGJAK002 is a Phase 2 trial aimed to assess the efficacy and safety of jaktinib 100 mg BID (N = 66) and 200 mg QD (N = 52) in JAK inhibitor-naive patients with intermediate- or high-risk MF. We herein present the long-term data with a median follow-up of 30.7 months. At data cutoff, 30.3% of patients in 100 mg BID and 28.8% in 200 mg QD were still continuing their treatment. The 100 mg BID group displayed a numerically higher best spleen response compared with the 200 mg QD group (69.7% vs. 46.2%), with 50.4% from the BID and 51.2% from the QD group maintaining spleen responses over 120 weeks. The 36-month survival rates were 78.2% in BID and 73.6% in QD group. The tolerability of jaktinib remained well, and common grade ≥3 adverse drug reactions included anemia (15.2% vs. 21.2%), thrombocytopenia (15.2% vs. 11.5%), and infectious pneumonia (10.6% vs. 1.9%) in BID and QD groups, respectively. By comparing the two groups, the incidence of adverse events (AEs) were similar, except for drug-related serious AEs (24.2% vs. 9.6%) and AEs leading to treatment discontinuation (15.2% vs. 7.7%), which were higher in BID group. The percentages of AEs resulting in death were comparable, with 6.1% in BID and 5.8% in QD group. These analyses further support the long-term durable efficacy and acceptable safety of jaktinib at 100 mg BID and 200 mg QD doses for treating MF.


Assuntos
Mielofibrose Primária , Humanos , Seguimentos , Mielofibrose Primária/tratamento farmacológico , Resultado do Tratamento
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 95-100, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322541

RESUMO

Disease control priority (DCP) is an important public health intervention strategy. Diseases that should be prioritized for prevention and control are first screened with a series of criteria, including the severity of the disease burden, the effectiveness of disease control technologies, the prevention and control capacity of the existing health system, etc. Then, the prevention and control technologies for these diseases undergo qualitative evaluation (eg, face-to-face interviews, expert consultation, workshops, etc) and quantitative evaluation (eg, cost-benefit analysis, multi-criteria decision analysis, etc). Finally, the public health initiatives that should be prioritized are identified. From the conception of the idea, to the formal proposition of the concept, to guidance for practice, DCP has gone through more than 70 years of development. Through DCP, significant contributions has been made to improving the efficiency of health care service systems and promoting the health of populations in developing countries. Herein, we systematically reviewed the background, development history, realization method, and practical applications of DCP, focusing on exploring the application potential of DCP in health governance and providing technical support and decision-making reference for the comprehensive promotion of the Healthy China Initiative.


Assuntos
Controle de Doenças Transmissíveis , Prioridades em Saúde , Saúde Pública , China , Nível de Saúde
15.
Skin Health Dis ; 4(1): e287, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38312255

RESUMO

Immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors combined with chemoradiotherapy shows great potential for cancer treatment and is getting extensively researched. However, a plethora of immune-related adverse events (irAEs) has been observed during anti-PD-1 treatment, including cutaneous adverse events, such as vitiligo and pruritus. These adverse events may lead to treatment discontinuation. When anti-PD-1 treatment is combined with radiotherapy (RT), irAEs may be exacerbated. Here we present a case report of an elderly patient with stage IIIb rectal cancer, who developed PD-1 inhibitor-associated vitiligo. After a session of RT, vitiligo lesions enlarged shortly thereafter. After discontinuation of anti-PD-1 treatment, vitiligo lesions and pruritus quickly improved with appropriate treatment. The rectal cancer achieved clinical complete response with no sign of recurrence or metastasis during follow-up. Considering the similar mechanism of anti-PD-1 treatment in targeting cancer and in inducing irAEs, cutaneous adverse events may be associated with favourable clinical response. Additionally, cutaneous irAEs aggravated by RT in this patient may suggested significant immune activation, which may occasionally contribute to tumour regression and favourable clinical outcome.

16.
Heliyon ; 10(2): e24408, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298693

RESUMO

Cervical cancer is a malignant tumor that occurs in the cervix of women and endangers their lives. In this study, we aimed to assess the roles of NUPR1 and TFE3 in cervical cancer. The Cancer Genome Atlas (TCGA) database was used to assess the correlation between NUPR1 and TFE3 expression in cervical cancer. By silencing NUPR1 and TFE3, and through 3-MA treatment, we determined whether their silencing could lead to lysosomal dysfunction, thereby inhibiting autophagy and cervical cancer cell proliferation. Their roles were further analyzed using molecular biological methods. Silencing NUPR1 and TFE3 inhibited cell proliferation and decreased the expression levels of autophagy-related genes, p62 and LC3B. By tracing lysosomes within cells, NUPR1 and TFE3 knockdown were found to induce lysosomal dysfunction, thereby inhibiting autophagy. In vivo experimental studies have shown that knockdown of NUPR1 and TFE3 can inhibit tumor growth, while reducing the ki67, p62, and LC3B expression levels and promoting apoptosis. Furthermore, the expression levels of lamp1 and lamp2, and the phosphorylation of PI3K (p-PI3K) and Akt (p-Akt) were significantly reduced after NUPR1 and TFE3 knockdown. However, treatment with 3-MA and overexpression of TFE3 could partially reverse the effect of silencing NUPR1. Overall, silencing NUPR1 reduced autophagy by inhibiting TFE3 in cervical cancer. Our results supply new evidence for the use of NUPR1 as a therapeutic target in cervical cancer.

17.
Photodiagnosis Photodyn Ther ; 46: 104022, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38401820

RESUMO

Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200-284 J/cm2 for cervical canal and the vaginal surfaces, 100-150 J/cm2 for cervix surface. Vaginal giant CA and LSIL lesions got complete remission at 6-month follow-up. Mild tolerable adverse reactions were observed after STBF-PDT and relieved in 24 h. Thus, the combination of Ho: YAG laser and STBF-PDT may be a novel option for cervical and vaginal giant CA and LSIL, especially for special vaginal fornix areas.

18.
Nat Commun ; 15(1): 1757, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413612

RESUMO

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Camundongos , Animais , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida albicans/metabolismo , Peptídeos/metabolismo
19.
Ren Fail ; 46(1): 2316259, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38345033

RESUMO

Acute kidney injury (AKI) can progress to renal fibrosis and chronic kidney disease (CKD), which reduces quality of life and increases the economic burden on patients. However, the molecular mechanisms underlying renal fibrosis following AKI remain unclear. This study tested the hypothesis that the Krüppel-like factor 4 (KLF4)/miR-101/Collagen alpha-1X (COL10A1) axis could inhibit epithelial-mesenchymal transition (EMT) and renal fibrosis after AKI in a mouse model of ischemia-reperfusion (I/R)-induced renal fibrosis and HK-2 cells by gene silencing, overexpression, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) and ELISA. Compared with the Sham group, I/R induced renal tubular and glomerular injury and fibrosis, and increased the levels of BUN, serum Scr and neutrophil gelatinase-associated lipocalin (NGAL), Col10a1 and Vimentin expression, but decreased E-cadherin expression in the kidney tissues of mice at 42 days post-I/R. Similarly, hypoxia promoted fibroblastic morphological changes in HK-2 cells and enhanced NGAL, COL10A1, Vimentin, and α-SMA expression, but reduced E-cadherin expression in HK-2 cells. These pathological changes were significantly mitigated in COL10A1-silenced renal tissues and HK-2 cells. KLF4 induces miR-101 transcription. More importantly, hypoxia upregulated Vimentin and COL10A1 expression, but decreased miR-101, KLF4, and E-cadherin expression in HK-2 cells. These hypoxic effects were significantly mitigated or abrogated by KLF4 over-expression in the HK-2 cells. Our data indicate that KLF4 up-regulates miR-101 expression, leading to the downregulation of COL10A1 expression, inhibition of EMT and renal fibrosis during the pathogenic process of I/R-related renal fibrosis.


Assuntos
Injúria Renal Aguda , MicroRNAs , Humanos , Camundongos , Animais , MicroRNAs/metabolismo , Lipocalina-2 , Vimentina/metabolismo , Fator 4 Semelhante a Kruppel , Hibridização in Situ Fluorescente , Qualidade de Vida , Caderinas/metabolismo , Injúria Renal Aguda/genética , Transição Epitelial-Mesenquimal , Colágeno/metabolismo , Fibrose , Hipóxia
20.
Photodiagnosis Photodyn Ther ; 46: 103999, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38336151

RESUMO

BACKGROUND: High recurrence rate of mild-to-moderate acne vulgaris following traditional therapy poses a significant challenge. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) with intense pulsed light (IPL) has emerged as a promising intervention. OBJECTIVES: This study aimed to evaluate the efficacy and safety of IPL-PDT for the treatment of mild-to-moderate acne vulgaris. METHODS: In this prospective, self-controlled study, eligible patients aged from 18 to 45 years old with Pillsbury grade Ⅰ-III facial acne were included. Patients were treated with three sessions of IPL-PDT at three-week interval, with follow-ups at 3 weeks and 2 months after the final treatment. RESULTS: A total of 31 patients were enrolled. At 3 weeks post-treatment, the mean count of acne lesions decreased significantly (P < 0.001), with 87.1 % of patients achieving treatment success (defined as ≥ 75 % clearance rate of acne lesions). Recurrence rate at 2-month follow-up was 9.68 %. No severe adverse reactions were observed. LIMITATIONS: This study is a single-center, self-controlled study. Multi-center study designed as randomize controlled trials involving a larger patient cohort is necessary. CONCLUSIONS: IPL-PDT is a promising therapy for mild-to-moderate acne vulgaris, exhibiting high efficacy, minimal adverse effects, and a low recurrence rate.

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