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1.
Skin Res Technol ; 30(5): e13720, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38743384

RESUMO

BACKGROUND: Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. MATERIALS AND METHODS: A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin. RESULTS: Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures. CONCLUSION: These results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.


Assuntos
Claudina-5 , Queratinócitos , MicroRNAs , Permeabilidade , Humanos , MicroRNAs/metabolismo , MicroRNAs/genética , Claudina-5/genética , Claudina-5/metabolismo , Feminino , Masculino , Queratinócitos/metabolismo , Estudos Retrospectivos , Adulto , Pele/metabolismo
2.
Int Immunopharmacol ; 134: 112139, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38739978

RESUMO

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.

3.
Clin Cosmet Investig Dermatol ; 17: 847-851, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633469

RESUMO

We report a case of rash in a 35-year-old female presenting with erythematous papules and infiltrative plaques on the nose and upper jaw resembling rosacea. The patient had been experiencing these symptoms for one year. A pathological biopsy revealed an inflammatory infiltrate consisting of dense perivascular lymphocytes surrounding hair follicles and sweat glands in the dermis. Immunohistochemistry demonstrated a predominance of CD4+ T cells compared to CD8+ T cells. Based on the clinical manifestations, histopathology, and immunohistochemistry, the patient was diagnosed with Jessner's Lymphocytic infiltration of the skin (JLIS). The patient was treated with oral Minocycline, 100mg twice daily. After 4 weeks, the dosage was reduced by half and the treatment continued for 2 months, resulting in complete resolution of the rash. The clinical presentation resembled rosacea, and this particular manifestation of JLIS has not been previously reported. Treatment with minocycline yielded satisfactory efficacy, and no recurrence has been observed for 5 year.

4.
J Cell Physiol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646844

RESUMO

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

5.
J Ethnopharmacol ; 330: 118194, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38641077

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prinsepia utilis Royle, native to the Himalayan region, has a long history of use in traditional medicine for its heat-clearing, detoxification, anti-inflammatory, and analgesic properties. Oils extracted from P. utilis seeds are also used in cooking and cosmetics. With the increasing market demand, this extraction process generates substantial industrial biowastes. Recent studies have found many health benefits with using aqueous extracts of these biowastes, which are also rich in polysaccharides. However, there is limited research related to the reparative effects of the water extracts of P. utilis oil cakes (WEPUOC) on disruptions of the skin barrier function. AIM OF THE STUDY: This study aimed to evaluate the reparative efficacy of WEPUOC in both acute and chronic epidermal permeability barrier disruptions. Furthermore, the study sought to explore the underlying mechanisms involved in repairing the epidermal permeability barrier. MATERIALS AND METHODS: Mouse models with induced epidermal disruptions, employing tape-stripping (TS) and acetone wiping (AC) methods, were used. The subsequent application of WEPUOC (100 mg/mL) was evaluated through various assessments, with a focus on the upregulation of mRNA and protein expression of Corneocyte Envelope (CE) related proteins, lipid synthase-associated proteins, and tight junction proteins. RESULTS: The polysaccharide was the major phytochemicals of WEPUOC and its content was determined as 32.2% by the anthranone-sulfuric acid colorimetric method. WEPUOC significantly reduced transepidermal water loss (TEWL) and improved the damaged epidermal barrier in the model group. Mechanistically, these effects were associated with heightened expression levels of key proteins such as FLG (filaggrin), INV (involucrin), LOR (loricrin), SPT, FASN, HMGCR, Claudins-1, Claudins-5, and ZO-1. CONCLUSIONS: WEPUOC, obtained from the oil cakes of P. utilis, is rich in polysaccharides and exhibits pronounced efficacy in repairing disrupted epidermal barriers through increased expression of critical proteins involved in barrier integrity. Our findings underscore the potential of P. utilis wastes in developing natural cosmetic prototypes for the treatment of diseases characterized by damaged skin barriers, including atopic dermatitis and psoriasis.


Assuntos
Epiderme , Extratos Vegetais , Proteínas de Junções Íntimas , Regulação para Cima , Animais , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas de Junções Íntimas/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Regulação para Cima/efeitos dos fármacos , Água/química , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Masculino , Ácido Graxo Sintases/metabolismo , Ácido Graxo Sintases/genética , Permeabilidade/efeitos dos fármacos
6.
Skin Res Technol ; 30(3): e13616, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38424730

RESUMO

OBJECTIVE: To investigate the life, sleep quality and anxiety of rosacea patients in Yunnan and the improvement of these aspects after treatment. METHODS: A total of 141 patients with rosacea and 123 healthy controls were included in our study. The quality of life, sleep quality and anxiety of patients with rosacea and healthy controls were investigated by the Rosacea Severity Scores (RSSs), the Medical Outcomes Study 36-item short-form health survey (SF-36), the Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS). The quality of life, sleep quality and anxiety of patients with rosacea were assessed again after treatment. RESULTS: Compared with healthy controls, patients with rosacea had significantly lower physical component scores (PCS) and mental component scores (MCS) but higher PSQI and SAS scores. After treatment, rosacea patients showed significantly higher MCS but lower PSQI and SAS scores. Correlation analysis showed a significant correlation between PCS, MCS, PSQI, SAS and RSSs. CONCLUSIONS: Patients with rosacea have a lower quality of life and sleep quality and tend to be more anxious than healthy controls. In addition, the mental quality of life, sleep quality and anxiety of rosacea patients can be significantly improved after treatment. Therefore, it is important to pay attention to the psychological status of rosacea patients. Psychological counseling and intervention are necessary to better prevent and treat rosacea.


Assuntos
Qualidade de Vida , Transtornos do Sono-Vigília , Humanos , Qualidade de Vida/psicologia , Estudos Retrospectivos , Qualidade do Sono , Transtornos do Sono-Vigília/psicologia , China/epidemiologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Sono
7.
Brain Inj ; 38(3): 194-201, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38297513

RESUMO

AIM: To explore the potential role of microRNA miR-221-5p on the angiopoietin-1 (Ang-1)/Ang-2/Tie-2 signaling axis after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Aspects of the rat's behavior were measured using the Kaoutzanis scoring system to test neurological responses. This included feeding behavior, body contraction, motor, and eye-opening responses. Brain sections were studied using transmission electron microscopy and Evans blue extravasation. Levels of Ang-1, Ang-2, and Tie-2 were determined by Western blot, while miR-221-5p was quantified using stem-loop real-time quantitative PCR (RT-qPCR). RESULTS: The SAH group responded worse to the neurological response test than the sham-operated group. The intercellular space was widened in the SAH group, but not in the sham-operated group. Evans blue dye leaked significantly more into brain tissue cells of the SAH group. Stem-loop qRT-PCR showed elevated miR-221-5p levels. Additionally, Ang-1 and Tie-2 were reduced but Ang-2 expression was increased after SAH. This led to a significant reduction of the Ang-1/Ang-2 ratio in the brain tissue, which was associated with the destruction of the blood-brain barrier. CONCLUSION: The data indicate that miR-221-5p might regulate blood-brain barrier dysfunction through the Ang-1/Ang-2/Tie-2 signaling axis, suggesting that it should be further investigated as a potential novel biomarker.


Assuntos
MicroRNAs , Hemorragia Subaracnóidea , Ratos , Animais , Barreira Hematoencefálica , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Azul Evans/metabolismo , MicroRNAs/metabolismo
8.
World J Urol ; 42(1): 36, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217714

RESUMO

PURPOSE: This prospective study aimed to explore the microstructural alterations of the white matter in overactive bladder syndrome (OAB) using the Tract-based Spatial Statistics (TBSS) method of diffusion kurtosis imaging (DKI). METHODS: A total of 30 patients were enrolled and compared with 30 controls. White matter (WM) status was assessed using tract-based spatial statistics for DKI. The differences in DKI-derived parameters, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), mean diffusivity (MD), radial kurtosis (RK), axial kurtosis (AK), axial diffusivity (AD), and radial diffusivity (RD), were compared between the two groups using the TBSS method. The correlation between the altered DKI-derived parameters and the (OABSS) scores was analyzed. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of different white matter parameters. RESULTS: As a result, compared with the HC group, the KFA, and FA values decreased significantly in the OAB group. Compared with the HC group, the MK and MD values increased significantly in the OAB group. The KFA values of the genu of corpus callosum (GCC) were significantly correlated with the OABSS scores (r = - 0.509; p = 0.004). The FA values of anterior corona radiata (ACR) were significantly correlated with OABSS scores (r = - 0.447; p = 0.013). The area under the ROC curve (AUC) for the genu of corpus callosum KFA values was higher than FA for the diagnosis of OAB patients. CONCLUSION: DKI is a promising approach to the investigation of the pathophysiology of OAB and a potential biomarker for clinical diagnosis of OAB.


Assuntos
Bexiga Urinária Hiperativa , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Estudos Prospectivos , Bexiga Urinária Hiperativa/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo
9.
J Cosmet Dermatol ; 23(3): 1009-1014, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059312

RESUMO

BACKGROUND: Sensitivity skin (SS) is a common skin disorders, which have a various of clinical manifestation. Facial erythema is common objective symptom of SS. However, the reasons for the occurrence of erythema in sensitive skin are not fully understood. AIMS: In this study, we preliminarily explain the possible factors inducing erythema of sensitive skin by evaluating facial erythematous reaction to lactic acid sting test (LAST) and capsaicin test (CAT) in subjects with sensitive skin. METHODS: A total of 197 subjects were divided into five groups, that is, normal controls (NC), LAST-positive (LAST+ ), both LAST and CAT positive (L+ C+ ), both LAST and CAT negative (L- C- ) and CAT-positive (CAT+ ). Erythema index (EI), a* value, and tissue viability imaging (TIVI) were measured before and after LAST and CAT, The ΔEI, Δa*, and ΔTIVI before and after LAST and CAT were calculated, and the correlation between the scores of CAT, EI values, a* values, and TIVI values were analyzed to clarify the causes of facial erythema. RESULTS: Our results showed that EI values and a* values were significantly higher in the L+ C+ and CAT+ group than in NC group, TIVI values were higher in the L+ C+ group than in NC group. ΔEI and Δa* values after LAST did not differ significantly among five groups. However, ΔEI values in L+ C+ group were higher than that in L- C- group, while Δa* values were higher in CAT+ group than in NC. Moreover, ΔTIVI values in L+ C+ group and CAT+ group were also significantly higher than that in NC group after capsaicin stimulation. CAT scores correlated positively with EI, a* and TIVI values. CONCLUSION: Our results suggest that sensitive skin subjects with positive CAT are more likely to experience erythema reactions, and vasodilation is more pronounced after capsaicin stimulation. Reducing vascular and neural hyperreactivity could be therapeutic target in management of facial erythema in subjects with sensitive skin.


Assuntos
Capsaicina , Eritema , Humanos , Capsaicina/efeitos adversos , Eritema/induzido quimicamente , Eritema/diagnóstico , Ácido Láctico
10.
J Environ Manage ; 350: 119597, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38029495

RESUMO

Due to the limitations of traditional ultraviolet (UV) in microbial inactivation in water, it is necessary to explore a more suitable and efficient UV disinfection method. In this study, an electron beam excitation multi-wavelength ultraviolet (EBE-MW-UV) system was established and aims to analyze its differential microbial inactivation capabilities in comparison to single-wavelength UV-LEDs in waterborne applications. Furthermore, the inactivation mechanisms of this system on microorganisms were explored. The results showed that EBE-MW-UV had significantly higher inactivation effects on the Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans in water compared to UV-LEDs (p<0.05), and the inactivation effect of EBE-MW-UV on Escherichia coli and Pseudomonas aeruginosa at the same UV dose was 3.8 and 1.9 log higher than that of UV-LEDs, respectively, EBE-MW-UV exhibited better inactivation effects on Gram-negative bacteria. Further research found that, under the majority of irradiation doses, neither EBE-MW-UV nor UV-LEDs were significantly affected by the concentration of suspended solids (5 and 20 mg/L) or humic acids (2 and 5 mg/L) in the water. Mechanism analysis revealed that during the disinfection process of EBE-MW-UV, microbial DNA and proteins were initially damaged, which prevented the occurrence of dark repair and led to bacterial inactivation. In addition, UV irradiation led to the production of additional reactive oxygen species (ROS) inside the cells, increasing cell membrane permeability and exacerbating membrane damage. This was accompanied by a decrease in energy metabolism and depletion of ATP, ultimately resulting in microbial inactivation. Therefore, EBE-MW-UV demonstrated more effective disinfection than single-wavelength UV-LEDs, showing great potential. Our research gives new insights into the characteristics of multiple wavelength ultraviolet, and provides scientific basis for the selection of new light sources in the field of ultraviolet disinfection.


Assuntos
Purificação da Água , Água , Elétrons , Purificação da Água/métodos , Microbiologia da Água , Raios Ultravioleta , Escherichia coli , Desinfecção/métodos
11.
PLoS One ; 18(12): e0295446, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38096251

RESUMO

OBJECTIVE: To analyze the influence path of the interaction between the unit environment, achievement transformation willingness, and achievement transformation cognition on achievement transformation output to provide a basis for optimizing the achievement transformation environment of medical and health institutions and improving the efficiency of scientific and technological achievements transformation. METHODS: Through the questionnaire survey, 292 data points were obtained. SPSS20.0 was used to conduct cross-table chi-square analysis and binary logistic regression analysis on the willingness, cognition, and output of scientific and technological achievements transformation. The process 14.0 plug-in is used to analyze the mediating effect of transformation cognition and the moderating effect of the unit environment. RESULTS: Achievement transformation willingness has a significant positive impact on achievement transformation cognition and achievement transformation output. Achievement transformation cognition has a positive impact on achievement transformation output, and the mediating effect of transformation cognition is significant and partial. The unit environment has a negative moderating effect on the influence of achievement transformation willingness on achievement transformation cognition, and a positive moderating effect on the influence of achievement transformation willingness on achievement transformation output. CONCLUSION: Personal factors and unit achievement transformation environment have an obvious influence on the willingness and cognition of achievement transformation. It is necessary to optimize the environment of unit scientific and technological achievements transformation, improve the policy system of benefiting from the achievements of scientific and technological achievements transformation of medical and health personnel, implement the disposal right, income right and distribution right of scientific and technological achievements transformation of medical and health institutions, and stimulate the enthusiasm of scientific and technological achievements transformation of medical and health personnel.


Assuntos
Cognição , Tecnologia , Logro , Inquéritos e Questionários
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(12): 1274-1280, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38149389

RESUMO

OBJECTIVE: To investigate the clinical value of analgesia and sedation under bispectral index (BIS) monitoring combined with hydraulic coupled intracranial pressure (ICP) monitoring in severe craniocerebral injury (sTBI). METHODS: (1) A prospective self-controlled parallel control study was conducted. A total of 32 patients with sTBI after craniotomy admitted to the intensive care unit (ICU) of the First People's Hospital of Huzhou from December 2020 to July 2021 were selected as the research objects. ICP was monitored by Codman monitoring system and hydraulically coupled monitoring system, and the difference and correlation between them were compared. (2) A prospective randomized controlled study was conducted. A total of 108 sTBI patients admitted to the ICU of the First People's Hospital of Huzhou from August 2021 to August 2022 were selected patients were divided into 3 groups according to the random number table method. All patients were given routine treatment after brain surgery. On this basis, the ICP values of the patients in group A (35 cases) were monitored by Codman monitoring system, the ICP values of the patients in group B (40 cases) were monitored by hydraulic coupling monitoring system, and the ICP values of the patients in group C (33 cases) were monitored combined with hydraulic coupling monitoring system, and the analgesia and sedation were guided by BIS. The ICP after treatment, cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, complications and Glasgow outcome score (GOS) at 6 months after surgery were compared among the 3 groups. In addition, patients in group B and group C were further grouped according to the waveforms. If P1 = P2 wave or P2 and P3 wave were low, they were classified as compensatory group. If the round wave or P2 > P1 wave was defined as decompensated group, the GOS scores of the two groups at 6 months after operation were compared. RESULTS: (1) There was no significant difference in ICP values measured by Codman monitoring system and hydraulic coupling monitoring system in the same patient (mmHg: 11.94±1.76 vs. 11.88±1.90, t = 0.150, P = 0.882; 1 mmHg≈0.133 kPa). Blan-altman analysis showed that the 95% consistency limit (95%LoA) of ICP values measured by the two methods was -4.55 to 4.68 mmHg, and all points fell within 95%LoA, indicating that the two methods had a good correlation. (2) There were no significant differences in cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, and incidence of complications such as intracranial infection, intracranial rebleeding, traumatic hydrocephalus, cerebrospinal fluid leakage, and accidental extubation among the 3 groups of sTBI patients (P > 0.05 or P > 0.017). The ICP value of group C after treatment was significantly lower than that of group A and group B (mmHg: 20.94±2.37 vs. 25.86±3.15, 26.40±3.09, all P < 0.05), the incidence of pulmonary infection (9.1% vs. 45.7%, 42.5%), seizure (3.0% vs. 31.4%, 30.0%), reoperation (3.0% vs. 31.4%, 40.0%), and poor prognosis 6 months after operation (33.3% vs. 65.7%, 65.0%) were significantly lower than those in group A and group B (all P < 0.017). According to the hydraulic coupling waveform, GOS scores of 35 patients in the compensated group were significantly higher than those of 38 patients in the decompensated group 6 months after operation (4.03±1.18 vs. 2.39±1.50, t = 5.153, P < 0.001). CONCLUSIONS: The hydraulic coupled intracranial pressure monitoring system has good accuracy and consistency in measuring ICP value, and it can better display ICP waveform changes than the traditional ICP monitoring method, and has better prediction value for prognosis evaluation, which can replace Codman monitoring to accurately guide clinical work. In addition, analgesia and sedation under BIS monitoring combined with hydraulic coupled ICP monitoring can effectively reduce ICP, reduce the incidence of complications, and improve the prognosis, which has high clinical application value.


Assuntos
Analgesia , Traumatismos Craniocerebrais , Humanos , Pressão Intracraniana , Estudos Prospectivos , Monitorização Fisiológica/métodos , Vazamento de Líquido Cefalorraquidiano
13.
Signal Transduct Target Ther ; 8(1): 397, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37848417

RESUMO

Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour treatment. The current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing (WGS) and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules, ignoring other peptide-presenting related steps. This may result in a gap between high prediction accuracy and relatively low clinical effectiveness. In this study, we designed an integrated in-silico pipeline, Neo-intline, which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation model. Validation on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma level. Furthermore, by taking the mouse melanoma model as an example, we verified the effectiveness of 20 neoantigens, including 10 MHC-I and 10 MHC-II peptides. The in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4+ T cells and CD8+ T cells to induce a T-cell-mediated cellular immune response. Moreover, although the therapeutic effect of neoantigen vaccines alone is not sufficient, combinations with other specific therapies, such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor (GM-CSF) and polyinosinic-polycytidylic acid (poly(I:C)), or immune checkpoint inhibitors, such as PD-1/PD-L1 antibodies, can illustrate significant anticancer effects on melanoma. Neo-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.


Assuntos
Melanoma , Vacinas , Animais , Camundongos , Linfócitos T CD8-Positivos , Epitopos de Linfócito T/metabolismo , Epitopos de Linfócito T/uso terapêutico , Antígenos de Neoplasias/metabolismo , Melanoma/terapia , Melanoma/tratamento farmacológico , Peptídeos
14.
J Exp Med ; 220(12)2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37851372

RESUMO

Infection is able to promote innate immunity by enhancing a long-term myeloid output even after the inciting infectious agent has been cleared. However, the mechanisms underlying such a regulation are not fully understood. Using a mouse polymicrobial peritonitis (sepsis) model, we show that severe infection leads to increased, sustained myelopoiesis after the infection is resolved. In post-infection mice, the tissue inhibitor of metalloproteinases 1 (TIMP1) is constitutively upregulated. TIMP1 antagonizes the function of ADAM10, an essential cleavage enzyme for the activation of the Notch signaling pathway, which suppresses myelopoiesis. While TIMP1 is dispensable for myelopoiesis under the steady state, increased TIMP1 enhances myelopoiesis after infection. Thus, our data establish TIMP1 as a molecular reporter of past infection in the host, sustaining hyper myelopoiesis and serving as a potential therapeutic target for modulating HSPC cell fate.


Assuntos
Hematopoese , Sepse , Animais , Camundongos , Diferenciação Celular , Imunidade Inata , Mielopoese , Inibidor Tecidual de Metaloproteinase-1/genética
15.
BMC Infect Dis ; 23(1): 720, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875791

RESUMO

BACKGROUND: Intestinal infectious diseases (IIDs) are a significant public health issue in China, and the incidence and distribution of IIDs vary greatly by region and are affected by various factors. This study aims to describe the spatio-temporal trends of IIDs in the Chinese mainland and investigate the association between socioeconomic and meteorological factors with IIDs. METHODS: In this study, IIDs in mainland China from 2006 to 2017 was analyzed using data obtained from the China Center for Disease Control and Prevention. Spatio-temporal mapping techniques was employed to visualize the spatial and temporal distribution of IIDs. Additionally, mean center and standard deviational ellipse analyses were utilized to examine the spatial trends of IIDs. To investigate the potential associations between IIDs and meteorological and socioeconomic variables, spatiotemporal zero-inflated Poisson and negative binomial models was employed within a Bayesian framework. RESULTS: During the study period, the occurrence of most IIDs has dramatically reduced, with uneven reductions in different diseases. Significant regional differences were found among IIDs and influential factors. Overall, the access rate to harmless sanitary toilets (ARHST) was positively associated with the risk of cholera (RR: 1.73, 95%CI: 1.08-2.83), bacillary dysentery (RR: 1.32, 95%CI: 1.06-1.63), and other intestinal infectious diseases (RR: 1.88, 95%CI: 1.52-2.36), and negatively associated with typhoid fever (RR: 0.66, 95%CI: 0.51-0.92), paratyphoid fever (RR: 0.71, 95%CI: 0.55-0.92). Urbanization is only associated with hepatitis E (RR: 2.48, 95%CI: 1.12-5.72). And GDP was negatively correlated with paratyphoid fever (RR: 0.82, 95%CI: 0.70-0.97), and bacillary dysentery (RR: 0.77, 95%CI: 0.68-0.88), and hepatitis A (RR: 0.84, 95%CI: 0.73-0.97). Humidity showed positive correlation with some IIDs except for amoebic dysentery (RR: 1.64, 95%CI: 1.23-2.17), while wind speed showed a negative correlation with most IIDs. High precipitation was associated with an increased risk of typhoid fever (RR: 1.52, 95%CI: 1.09-2.13), and high temperature was associated with an increased risk of typhoid fever (RR: 2.82, 95%CI: 2.06-3.89), paratyphoid fever (RR: 2.79, 95%CI: 2.02-3.90), and HMFD (RR: 1.34, 95%CI: 1.01-1.77). CONCLUSIONS: This research systematically and quantitatively studied the effect of socioeconomic and meteorological factors on IIDs, which provided causal clues for future studies and guided government planning.


Assuntos
Doenças Transmissíveis , Disenteria Bacilar , Enteropatias , Infecções Intra-Abdominais , Febre Paratifoide , Febre Tifoide , Humanos , Disenteria Bacilar/epidemiologia , Febre Tifoide/epidemiologia , Febre Paratifoide/epidemiologia , Teorema de Bayes , Análise Espaço-Temporal , China/epidemiologia , Enteropatias/epidemiologia , Incidência , Doenças Transmissíveis/epidemiologia
16.
Am J Transl Res ; 15(9): 5613-5623, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854212

RESUMO

OBJECTIVE: To investigate the effect of early, repeated hemoperfusion in conjunction with hemodialysis on the health status, blood-gas indices, and prognosis of patients with paraquat (PQ) poisoning. METHODS: In this retrospective study, clinical data of 149 PQ-poisoned patients treated at Xianyang First People's Hospital between January 2019 and January 2022 were analysed. Sixty-two patients who received conventional treatment coupled with early, repeated hemoperfusion were designated as the control group. The remaining 87 patients, who were subjected to additional hemodialysis on the basis of the control group, were designated in the experimental group. A comparison was made between the two groups regarding the changes in liver function, renal function, and blood-gas indices before and after the treatment. Three-month survival outcomes of both groups were analyzed using Cox regression, with survival curves drawn for different prognostic factors. RESULTS: The experimental group exhibited significantly lower levels of indirect bilirubin (IBiL) and glutamic-pyruvic transaminase (ALT) after the treatment compared to the control group (all P < 0.05), as well as markedly lower levels of total bilirubin (TBil), direct bilirubin (DBil), glutamic-oxaloacetic transaminase (AST), alkaline phosphatase (ALP), urea nitrogen (BUN), and creatinine (Cr) (all P < 0.01). The experimental group also demonstrated significantly improved arterial partial pressure of oxygen (PaO2) and PaO2/inspired oxygen (FIO2) ratios, along with reduced arterial carbon dioxide partial pressure (PaCO2) after the treatment (all P < 0.05). Moreover, a significantly higher three-month survival rate was observed in the experimental group compared to the control group (P < 0.001). According to Cox regression analysis, blood purification mode, age, urine PQ concentration upon admission, the timing of initial gastric lavage and bowl cleanse, and the timing of initial blood purification were identified as independent factors affecting the patients' 90-day prognosis. CONCLUSION: Early, repeated hemoperfusion coupled with hemodialysis significantly improves the blood-gas indices and liver and kidney function in patients with PQ poisoning, while also extending their short-term survival.

17.
Sci Rep ; 13(1): 12783, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550317

RESUMO

A recent surge of patent applications among public hospitals in China has aroused significant research interest. A country's healthcare innovation capacity can be measured by its number of patents. This paper explores the link between the number of patents and ten independent variables. Multicollinearity was carefully detected and removed by using the variable selection method and LASSO regression, respectively. The Poisson model and the negative binomial model were proposed to analyze the patent data. Three goodness of fit tests, the Pearson test, the deviance test, and the DHARMa non-parametric dispersion test, were conducted to investigate if the model has a good fit. After discovering four clusters by conducting agglomerative hierarchical clustering, these two models were replaced by the negative binomial mixed model. The likelihood ratio test was used to determine which model is more appropriate and the results reveal that the negative binomial mixed model outperforms both the Poisson model and the negative binomial model. Three variables, number of health technicians per 10,000 people, financial expenditure on science and technology as well as number of patent applications per 10,000 health personnel, have a significantly positive relationship with the number of patents in Chinese tertiary public hospitals.


Assuntos
Aprendizado de Máquina , Modelos Estatísticos , Humanos , Funções Verossimilhança , China , Análise por Conglomerados
18.
BMC Public Health ; 23(1): 1652, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644452

RESUMO

BACKGROUND: Despite significant progress in sanitation status and public health awareness, intestinal infectious diseases (IID) have caused a serious disease burden in China. Little was known about the spatio-temporal pattern of IID at the county level in Zhejiang. Therefore, a spatio-temporal modelling study to identify high-risk regions of IID incidence and potential risk factors was conducted. METHODS: Reported cases of notifiable IID from 2008 to 2021 were obtained from the China Information System for Disease Control and Prevention. Moran's I index and the local indicators of spatial association (LISA) were calculated using Geoda software to identify the spatial autocorrelation and high-risk areas of IID incidence. Bayesian hierarchical model was used to explore socioeconomic and climate factors affecting IID incidence inequities from spatial and temporal perspectives. RESULTS: From 2008 to 2021, a total of 101 cholera, 55,298 bacterial dysentery, 131 amoebic dysentery, 5297 typhoid, 2102 paratyphoid, 27,947 HEV, 1,695,925 hand, foot and mouth disease (HFMD), and 1,505,797 other infectious diarrhea (OID) cases were reported in Zhejiang Province. The hot spots for bacterial dysentery, OID, and HEV incidence were found mainly in Hangzhou, while high-high cluster regions for incidence of enteric fever and HFMD were mainly located in Ningbo. The Bayesian model showed that Areas with a high proportion of males had a lower risk of BD and enteric fever. People under the age of 18 may have a higher risk of IID. High urbanization rate was a protective factor against HFMD (RR = 0.91, 95% CI: 0.88, 0.94), but was a risk factor for HEV (RR = 1.06, 95% CI: 1.01-1.10). BD risk (RR = 1.14, 95% CI: 1.10-1.18) and enteric fever risk (RR = 1.18, 95% CI:1.10-1.27) seemed higher in areas with high GDP per capita. The greater the population density, the higher the risk of BD (RR = 1.29, 95% CI: 1.23-1.36), enteric fever (RR = 1.12, 95% CI: 1.00-1.25), and HEV (RR = 1.15, 95% CI: 1.09-1.21). Among climate variables, higher temperature was associated with a higher risk of BD (RR = 1.32, 95% CI: 1.23-1.41), enteric fever (RR = 1.41, 95% CI: 1.33-1.50), and HFMD (RR = 1.22, 95% CI: 1.08-1.38), and with lower risk of HEV (RR = 0.83, 95% CI: 0.78-0.89). Precipitation was positively correlated with enteric fever (RR = 1.04, 95% CI: 1.00-1.08), HFMD (RR = 1.03, 95% CI: 1.00-1.06), and HEV (RR = 1.05, 95% CI: 1.03-1.08). Higher HFMD risk was also associated with increasing relative humidity (RR = 1.20, 95% CI: 1.16-1.24) and lower wind velocity (RR = 0.88, 95% CI: 0.84-0.92). CONCLUSIONS: There was significant spatial clustering of IID incidence in Zhejiang Province from 2008 to 2021. Spatio-temporal patterns of IID risk could be largely explained by socioeconomic and meteorological factors. Preventive measures and enhanced monitoring should be taken in some high-risk counties in Hangzhou city and Ningbo city.


Assuntos
Doenças Transmissíveis , Disenteria , Febre Tifoide , Masculino , Humanos , Teorema de Bayes , China/epidemiologia , Doenças Transmissíveis/epidemiologia
19.
J Cosmet Dermatol ; 22(12): 3505-3510, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37464957

RESUMO

BACKGROUND: Although rosacea and seborrheic dermatitis share some symptoms of sensitive skin, whether they respond differently to lactic acid sting and capsaicin tests, common tests for diagnosis of sensitive skin, is unknown. OBJECTIVES: To reveal the cutaneous responses to lactic acid sting (LAST) and capsaicin test (CAT) in females with either rosacea vs. seborrheic dermatitis. METHODS: A total of 60 patients with rosacea, 20 patients with seborrheic dermatitis and 40 normal controls were enrolled in the study. Their skin sensitivity to stimuli were evaluated following topical application of either 10% lactic acid solution or 0.001% capsaicin solution. Transepidermal water loss (TEWL) rates and erythema indexes were also measured on the face. RESULTS: In comparison to normal controls, the positive rate to either LAST or CAT was significantly higher in subjects with rosacea (p < 0.001), but not in that with seborrheic dermatitis. Similarly, individuals with rosacea displayed a higher positive rate to both LAST and CAT than those with seborrheic dermatitis and normal controls (p < 0.001). In parallel, the LAST scores and CAT scores in individuals with rosacea were significantly higher than in that with either seborrheic dermatitis or normal controls (p < 0.001). The baseline TEWL rates and erythema indexes were higher in individual with rosacea than in normal controls (p < 0.001). But the baseline TEWL rates and erythema indexes did not differ significantly between subjects with rosacea and that with seborrheic dermatitis. Moreover, LAST scores and CAT scores correlated positively with TEWL (p < 0.0001). TEWL rates were higher in CAT positive than in CAT negative subjects (p < 0.0001). Finally, erythema index correlated positively with CAT scores (p < 0.0001), but not with LAST scores (p = 0.0842). CONCLUSIONS: Skin responses to LAST and CAT differ between individuals with rosacea and those with seborrheic dermatitis, possibly due to the differences in epidermal permeability barrier and the neurovascular hyperreactivity. The higher LAST and CAT scores, as well as positive rates of both LAST and CAT can be attributable to inferior permeability barrier and the neurovascular hyperreactivity in subjects with rosacea.


Assuntos
Dermatite Seborreica , Rosácea , Feminino , Humanos , Capsaicina/farmacologia , Dermatite Seborreica/diagnóstico , População do Leste Asiático , Eritema/diagnóstico , Ácido Láctico/farmacologia , Rosácea/diagnóstico , Pele , Testes Cutâneos
20.
Skin Res Technol ; 29(7): e13401, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37522494

RESUMO

BACKGROUND: The difference in skin pigmentation induced by blue light between melasma patients and healthy people has not been reported. This study aimed to explore the impact of different doses of blue light irradiation on the pigmentation of the skin of non-exposed areas in female melasma patients with III-IV-type skin and healthy women. MATERIALS AND METHODS: This observational study enrolled patients with melasma and healthy people at the First Affiliated Hospital of Kunming Medical University between January and April 2021. The outcomes were the degree of pigmentation, ΔL*, and ΔITA* values. RESULTS: Forty-two (21/group) participants were enrolled. After irradiation with different doses of blue light, different degrees of pigmentation could be observed in the irradiated area of the skin of female melasma patients and healthy women. The △L* and △ITA* values in the irradiated area of the skin of healthy women were higher than in female melasma patients after blue light irradiation at 20 J/cm2 (p < 0.05). There were no significant differences in the pigmentation scores, △L* values, and △ITA* values in the irradiated areas of skin at different time points after irradiation with the other doses of blue light (p > 0.05). CONCLUSION: Blue light at 20 J/cm2 induced a smaller change in pigmentation in melasma patients than in healthy women, but the effect of blue light at 40-80 J/cm2 was similar.


Assuntos
Melanose , Pigmentação da Pele , Humanos , Feminino , Luz , Pele/efeitos da radiação
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