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BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.
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Proteínas Ligadas por GPI , Lectinas , Hiperplasia Prostática , Animais , Masculino , Camundongos , Citocinas/genética , Citocinas/metabolismo , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Inflamação/patologia , Lectinas/genética , Lectinas/metabolismo , Extratos Vegetais/farmacologia , Próstata/metabolismo , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Fator de Necrose Tumoral alfaRESUMO
Anthropogenic emissions, originating from human activities, stand as the primary contributors to PM2.5, which is recognized as a global health threat. The disease burden associated with PM2.5 has been extensively documented. However, the prevailing estimations have predominantly relied on PM2.5 exposure-response functions, neglecting the distinct risks posed by PM2.5 from various sources. China has experienced a significant reduction in the PM2.5 concentration due to stringent emission controls. With diverse sources and abundant mortality data, this situation provides a unique opportunity to estimate short-term source-specific attributable mortality. Our approach involves an integrated unequal health risk-oriented modeling in China, incorporating a source-oriented Community Multiscale Air Quality model, an adjustment and downscaling method for exposure measurement, a generalized linear model with random-effects meta-analysis, and premature mortality estimation. Adhering to the unequal health risk concept, we calculated the attributable mortality of multiple PM2.5 sources by determining the source risk-adjusted factor. In this study, we observed varying excess risks associated with multiple PM2.5 sources, with transportation-related PM2.5 exhibiting the most substantial association. An interquartile range increase (7.65 µg/m3) was linked to a 1.98% higher daily nonaccidental mortality. Residential use- and transportation-related PM2.5 emerged as the two principal sources of premature mortality. In 2018, a remarkable 53,381 avoiding deaths were estimated compared to 2013, and over 67% of these were attributed to reductions in coal-dependent sources. Notably, transportation-related PM2.5 emerged as the largest contributor to premature mortality in 2018. This study underscores the significance of a new source-oriented health risk assessment to support actions aimed at reducing air pollution. It strongly advocates for heightened attention to PM2.5 reductions in the transportation sector in China.
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Poluentes Atmosféricos , Poluição do Ar , Material Particulado , China/epidemiologia , Humanos , Exposição Ambiental , Medição de RiscoRESUMO
Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.
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Poluentes Atmosféricos , Poluição do Ar , Material Particulado , Índia , Humanos , Poluentes Atmosféricos/análise , Exposição Ambiental , ClimaRESUMO
Air pollution exposure has been linked to a variety of adverse health outcomes among minors; yet little is known about the associated health inequity across regions and schools. Here, we assessed the unequal health burden linked to particulate matter exposure among minors of 10,358 schools in China through 12,439,232 individual health records. Our findings highlight the persistent health risks with superlinear concentration-response patterns and following inverted U-shaped risk trends, that each 10 µg/m3 increase in PM2.5 exposure resulted in 4.1% (3.9-4.2%) additional school absenteeism risk. Compared to urban well-built schools, minors in rural poor-built schools experienced significantly higher exposure and slower rate of risk reduction and had over 80.0% less medical resources while bearing 145.2% of the health burden. Disparities in pollution exposure, built environment, and resource allocation are intertwined to shape the health inequity pattern, especially between rural and urban schools. These findings underscore the urgency for persistent efforts aimed at disadvantaged schools to reduce pollution exposure and equitably distribute social resources, ultimately securing an impartial health-centered education for minors.
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Poluição do Ar , Humanos , China , Material Particulado , Instituições Acadêmicas , Adolescente , Exposição Ambiental , Criança , Poluentes Atmosféricos , Feminino , Masculino , População RuralRESUMO
BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Osteócitos , Osteogênese , Tropomiosina , Animais , Masculino , Camundongos , Adipogenia , Diferenciação Celular , Células Cultivadas , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Osteoclastos/metabolismo , Osteócitos/metabolismo , Osteoporose/metabolismo , Tropomiosina/metabolismo , Tropomiosina/genéticaRESUMO
Adults' emotional reactions to the pain and pleasure of others are influenced by the moral character of those individuals. However, it remains unclear whether children's emotional responses also show such selectivity. To investigate this, we compared 4- to 8-year-old children's emotional responses to the physical pain and pleasure of prosocial versus antisocial puppets. In Study 1, children reported unhappiness after witnessing the pain of the prosocial and antisocial puppets but reported less unhappiness after witnessing the pain of the antisocial puppet. In Study 2, children reported happiness after witnessing the pleasure of both puppets but reported being less happy for the antisocial puppet. These results suggest that children are less likely to empathize with antisocial individuals. Meanwhile, children did not display Schadenfreude (pleasure at others' pain) or Gluckschmerz (displeasure at others' pleasure) toward antisocial individuals in our studies. Moreover, the selectivity of children's emotional responses disappeared after we manipulated the physical competence rather than the moral character of the puppets in Study 3. Our findings help to reveal the moral selectivity of emotional responses to others' pleasure and pain during early childhood.
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Emoções , Empatia , Dor , Prazer , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Dor/psicologia , Princípios Morais , Comportamento SocialRESUMO
The small tree species Rhamnella franguloides, belonging to the genus Rhamnella in the tribe Rhamneae Hook. f. of Rhamnaceae (Hauenschild et al. 2016), is an important medicinal plant commonly used for making tea in China. In August 2023, leaf spot symptoms were observed on R. franguloides in Shangyao county, Yantai, Shandong, China, with a disease incidence of 45-65%. Initially appearing as small dark brown spots on the tip lesions, they later expanded and merged into irregular-shaped brown necrotic lesions with yellowish halos. To isolate pathogen, 20 symptomatic tissue fragments (5 × 5 mm) from ten sampling randomly plants were surface sterilized, placed on potato dextrose agar (PDA) plates, and incubated at 25°C in darkness for 3 days to obtain colonies.10 purified isolates with similar morphological characteristics were obtained by single-spore isolation from the colonies. The representative isolate MR13 was chosen for morphological and molecular analysis. The colonies On PDA medium initially appear as a circular yellow-brown ring with white round margins, ultimately turning into olive green with fluffy aerial hyphae. The conidiophores displayed brown pigmentation, solitary or branched, producing abundant short chains of conidia. The conidia were typically obclavate to obpyriform or ellipsoid in shape, 22.5-64.5 × 12.5-23.6µm in size, with a short conical beak at the apex, zero to three longitudinal septa and one to five transverse septa. Based on cultural and morphological characteristics, the fungus was identified as Alternaria spp (Simmons 2007). Due to morphological traits, five genes (the internal transcribed spacer [ITS], actin [ACT], plasma membrane ATPase [ATP], Alternaria major allergen [Alt a1] and histone 3 [H3]) form MR13 were amplified using primer pairs ITSI / ITS4, ACTDF1/R1, ATPDF1 / ATPDRI, Alt-for / Alt-rev, and H3-1a/1b, respectively (Hong et al. 2005; Lawrence et al. 2013; Lousie and Donaldson 1995). BLASTn analysis failed to confirm the identification of MR13 species based on ITS, ACT, ATP and Alt a1(ITS, OR668512; ACT, OR676918; ATP, OR676917; Alt a1, OR676919). The phylogenetic tree showed that it was closely related to Alternaria alternate, A. tenuissima, and A. destruens. The H3 sequence (OR676920) exhibited 100% similarity to A. tenuissima (OR485421). The phylogenetic tree constructed solely with H3 further confirmed MR13 as A. tenuissima. Pathogenicity tests were conducted by introducing the fungus onto healthy R. franguloides leaves in the field. Fifty leaves (five per plant) were treated with a 20ml suspension containing around 1x10^4 spores/ml, while an equal number of control samples were sprayed with distilled water. Transparent plastic bags were used to cover the treated leaves for 48 hours and maintain humidity. After fourteen days of inoculation, consistent leaf spotting symptoms were observed. In contrast, the control leaves showed no sign of infection. The fungal pathogen was successfully reisolated and identified as A. tenuissima through morphological and sequence analysis, fulfilling Koch's postulates. To our knowledge, this is the first report of A. tenuissima causing leaf spot disease on R. franguloides in China. Identifying the disease's causal agent is crucial for developing effective management strategies.
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OBJECTIVES: Psoriatic arthritis (PsA) is the most prevalent coexisting condition associated with psoriasis. Early-stage PsA patients always present unspecific and subtle clinical manifestations causing delayed diagnosis and leading to unfavorable health outcomes. The application of ultrasound enables precise identification of inflammatory changes in musculoskeletal structures. Hence, we constructed ultrasound models to aid early diagnosis of PsA. METHODS: This is a cross-sectional study carried out in the Department of Dermatology at West China Hospital (October 2018-April 2021). All participants underwent thorough ultrasound examinations. Participants were classified into the under 45 group (18 ≤ age ≤ 45) and over 45 group (age > 45) and then randomly grouped into derivation and test cohort (7:3). Univariable logistic regression, least absolute shrinkage and selection operator, and multivariable logistic regression visualized by nomogram were conducted in order. Receiver operating characteristic (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were performed for model verification. RESULTS: A total of 1256 participants were included, with 767 participants in the under 45 group and 489 in the over 45 group. Eleven and sixteen independent ultrasonic variables were finally selected to construct the under 45 and over 45 model with the area under the ROC of 0.83 (95%CI: 0.78-0.87) and 0.83 (95%CI: 0.78-0.88) in derivation cohort, respectively. The DCA and CICA analyses showed good clinical utility of the two models. CONCLUSION: The implementation of the ultrasound models could streamline the diagnostic process for PsA in psoriasis patients, leading to expedited evaluations while maintaining diagnostic accuracy.
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Aims: Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods: This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results: In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion: Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes.
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Ácido Hialurônico , Osteoartrite do Quadril , Plasma Rico em Plaquetas , Humanos , Injeções Intra-Articulares , Osteoartrite do Quadril/tratamento farmacológico , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Resultado do Tratamento , Anestésicos Locais/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Viscossuplementos/administração & dosagem , Metanálise em Rede , Medição da DorRESUMO
This article aims to analyze the prevalence of sarcopenia among the elderly in Guizhou Province, China, and its association with human immunodeficiency virus (HIV) infection. This cross-sectional study included 377 patients aged 60 and above in Guiyang Public Health Treatment Center from December 2022 to October 2023, including 231 patients in the community clinic and 146 HIV-infected individuals. According to the Asian Working Group for Sarcopenia 2019 Consensus to diagnose sarcopenia. Logistic regression was used to explore association between sarcopenia and HIV, and stratified by sex and age group. The prevalence of sarcopenia in the non-HIV infection elderly in Guizhou Province was 7.8% (21.3% in males and 5.5% in females), and the prevalence of sarcopenia in HIV-infected individuals was 29.5% (33.3% in males and 13.2% in females), with a statistically significant difference between HIV groups (χ2â =â 30.946, Pâ <â .001). After control of gender, age, body mass index, body fat percentage, hypertension, diabetes, taking statins, smoking status, medium to high-intensity physical activity, whether childhood poverty, and parents died young, HIV infection was significantly associated with sarcopenia in the elderly (odds ratio =â 4.635, 95% confidence interval â =â 1.920-11.188, Pâ =â .001). The results of stratified regression were similar to the main results. The prevalence of sarcopenia in the elderly population in China was severe. HIV infection was a risk factor for sarcopenia. It is urgent to establish a prevention and treatment system for sarcopenia in the elderly population, especially for elderly HIV-infected male.
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Infecções por HIV , Sarcopenia , Humanos , Masculino , Feminino , Sarcopenia/epidemiologia , China/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Prevalência , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
Long-term high altitudes (HA) exposure's impact on cognition has yielded inconsistent findings in previous research. To address this, we conducted a meta-analysis of 49 studies (6191 individuals) to comprehensively evaluate this effect. Moderating factors such as cognitive task type, altitude (1500-2500â¯m, 2500-4000â¯m, and above 4000â¯m), residential type (chronic and lifelong), adaptation level and demographic factors were analyzed. Cognitive tasks were classified into eight categories: perceptual processes, psychomotor function, long-term memory, working memory, inhibitory control, problem-solving, language, and others. Results revealed a moderate negative effect of HA on cognitive performance (g = -.40, SE =.18, 95% CI = -.76 to -.05). Psychomotor function and long-term memory notably experience the most pronounced decline, while working memory and language skills show moderate decreases due to HA exposure. However, perceptual processes, inhibitory control, and problem-solving abilities remain unaffected. Moreover, residing at altitudes above 4000â¯m and being a HA immigrant are associated with significant cognitive impairment. In summary, our findings indicate a selective adaptation of cognitive performance to HA conditions.
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Altitude , Cognição , Humanos , Cognição/fisiologia , Memória de Curto Prazo/fisiologiaRESUMO
Available evidence demonstrates that individuals with body-image disturbance (BID) are prone to suffer from depression. This systematic review provides, to our knowledge, the first synthesis of the psychological mechanism of the association between BID and depression. We conducted a thorough search of online databases, including PubMed, Web of Science, and PsycINFO, for articles published up until February 2024. The final analysis comprised a total of 23 studies that focused on the mediating or moderating effects of psychological factors between depression and BID. This review identifies self-esteem and social support as both mediators and moderators of the relationship between BID and depression, while perceived stress acted only as a mediator. High self-esteem and strong social support as well as low levels of perceived stress may help individuals experience lower levels of BID, thereby contributing to a decreased likelihood of depression. Interventions aimed at increasing self-esteem, developing strong support, and decreasing perceived stress may hold promise to reduce the risk of depression in those with BID.
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Depressão , Autoimagem , Apoio Social , Humanos , Depressão/psicologia , Estresse Psicológico/psicologia , Imagem Corporal/psicologia , Transtornos Dismórficos Corporais/psicologiaRESUMO
Previous studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients. IMPORTANCE: In this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions.
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Artrite Psoriásica , Microbioma Gastrointestinal , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/metabolismo , Eubacterium , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/metabolismo , FezesRESUMO
Objectives: This research first investigated the effect of mesoporous silica nanoparticles (nMS) carrying chlorhexidine and silver (nMS-nAg-Chx) on periodontitis-related biofilms. This study aimed to investigate (1) the antibacterial activity on Porphyromonas gingivalis (P. gingivalis) biofilm; (2) the suppressing effect on virulence of P. gingivalis biofilm; (3) the regulating effect on periodontitis-related multispecies biofilm. Methods: Silver nanoparticles (nAg) and chlorhexidine (Chx) were co-loaded into nMS to form nMS-nAg-Chx. Inhibitory zone test and minimum inhibitory concentration (MIC) against P. gingivalis were tested. Growth curves, crystal violet (CV) staining, live/dead staining and scanning electron microscopy (SEM) observation were performed. Biofilm virulence was assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Quantitative Real Time-PCR (qPCR) were performed to validate the activity and composition changes of multispecies biofilm (P. gingivalis, Streptococcus gordonii and Streptococcus sanguinis). Results: nMS-nAg-Chx inhibited P. gingivalis biofilm dose-dependently (p<0.05), with MIC of 18.75 µg/mL. There were fewer live bacteria, less biomass and less virulence in nMS-nAg-Chx groups (p<0.05). nMS-nAg-Chx inhibited and modified periodontitis-related biofilms. The proportion of pathogenic bacteria decreased from 16.08 to 1.07% and that of helpful bacteria increased from 82.65 to 94.31% in 25 µg/mL nMS-nAg-Chx group for 72 h. Conclusions: nMS-nAg-Chx inhibited P. gingivalis growth, decreased biofilm virulence and modulated periodontitis-related multispecies biofilms toward healthy tendency. pH-sensitive nMS-nAg-Chx inhibit the pathogens and regulate oral microecology, showing great potential in periodontitis adjunctive therapy.
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Smoking is by far one of the greatest public health threats and is recognized as an important predisposing factor for osteoporosis. Exposure to cigarette smoke (CS) has been reported to be associated with inflammation-associated diseases through the induction of pyroptosis. Nevertheless, the correlation between pyroptosis and bone loss induced by CS remains uninvestigated. Here, a mouse model of mainstream smoke exposure-induced osteoporosis was established. µCT, biomechanical testing, and immunohistochemical staining of bone tissue were used to assess the deleterious effects of CS on bone metabolism. In vitro, the effects of cigarette smoke extracts (CSE) on mouse primary bone marrow-derived mesenchymal stem cells (BMSCs) were tested by cell viability assays, gene and protein expression assays, and alizarin red staining. The utilization of the pyroptosis inhibitor MCC950 served to confirm the critical role of BMSCs pyroptosis in CS-induced osteoporosis. Our results indicated that exposure to mainstream smoke led to a notable decrease in the quantity of osteoblasts and hindered the process of osteogenic differentiation in mice. Additionally, there was a significant increase in the expression of pyroptosis-related proteins in the bone marrow. The inhibitory effects of CSE on cell viability and osteogenic differentiation of BMSCs were found to be dose-dependent in vitro. However, the presence of the pyroptosis inhibitor MCC950 significantly improved the impaired osteogenic differentiation and bone mineralization caused by CSE. These results highlight the crucial involvement of BMSCs pyroptosis in the development of bone loss induced by CS. In summary, the findings of this study provide novel evidence that CS exerts a detrimental effect on the process of osteogenesis in BMSCs through the induction of pyroptosis, ultimately leading to bone loss. Inhibition of pyroptosis effectively attenuated the toxicological effects of CS on BMSCs, providing a new target for preventing inflammatory osteoporosis.
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The therapeutic strategy for the treatment of pemphigus vulgaris (PV) still needs optimization because of the multiple deficiencies of glucocorticoid and rituximab. Ofatumumab, another CD20 monoclonal antibody administrated subcutaneously, provides a possible alternative option. In this study, three patients experienced PV relapse after clinical remission induced by rituximab. With written informed consent, they received an ofatumumab (20 mg) subcutaneous injection twice (2 weeks apart) in combination with a prednisone dose adjusted according to their weight and disease severity. Over the 24-week observation, two of three patients achieved lesion clear-up under prednisone (0.2 mg/kg per day), and the other patient's pemphigus disease area index dropped from 39 to 3 with prednisone (15 mg/day). The anti-desmoglein antibody levels and CD19+B cell counts declined compared to those at baseline. No severe adverse events were observed within the 24-week follow-up. In summary, we propose a protocol of ofatumumab for patients with refractory PV and report positive treatment outcomes of three patients who received this regimen.
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Anticorpos Monoclonais Humanizados , Pênfigo , Recidiva , Rituximab , Humanos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Quimioterapia Combinada/métodos , Glucocorticoides/administração & dosagem , Injeções Subcutâneas , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Pênfigo/imunologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).
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BACKGROUND: Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved. OBJECTIVES: To investigate the efficacy and safety of low-dose RTX (a single infusion of 500 mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX. METHODS: Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected. RESULTS: Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone. CONCLUSIONS: This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV.
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Doenças Autoimunes , Pênfigo , Humanos , Pênfigo/tratamento farmacológico , Estudos de Coortes , Rituximab/efeitos adversos , Resposta Patológica Completa , CorticosteroidesRESUMO
Despite the tremendous progress of chimeric antigen receptor T (CAR-T) cell therapy in hematological malignancies, their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment (TME) and systemic toxicity caused by excessive cytokine release. As a key regulator of the immunosuppressive TME, TGF-ß promotes cytokine synthesis via the NF-κB pathway. Here, we coexpressed SMAD7, a suppressor of TGF-ß signaling, with a HER2-targeted CAR in engineered T cells. These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-ß-triggered exhaustion, which enabled sustained tumoricidal capacity after continuous antigen exposure. Moreover, SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells. Mechanistically, SMAD7 downregulated TGF-ß receptor I and abrogated the interplay between the TGF-ß and NF-κB pathways in CAR-T cells. As a result, these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-ß. SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids. Therefore, our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Animais , Humanos , Camundongos , Citocinas/metabolismo , Imunoterapia Adotiva , Neoplasias/terapia , NF-kappa B/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Proteína Smad7/genética , Proteína Smad7/metabolismo , Linfócitos T , Fator de Crescimento Transformador beta/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Trigeminal neuralgia (TN) is difficult to treat due to its severe pain intensity and recurring episodes, which significantly impact quality of life. OBJECTIVES: We aimed to assess the effectiveness of electroacupuncture (EA) in alleviating the pain intensity in TN, and to determine whether EA combined with low-dosage carbamazepine (CBZ) has a synergistic effect. METHODS: A multi-centre, randomized, 2 × 2 factorial trial was conducted. Participants who met the inclusion criteria received active EA or sham EA for 60 min, three times a week for four weeks; CBZ (300 mg per day) or placebo for four weeks. The primary outcome was the change in visual analog scale (VAS) score from baseline to weeks 2, 4, 16, and 28. Secondary outcomes included quality of life and adverse events. RESULTS: A total of 120 participants (75 females and 45 males; mean (SD) age, 58.5 (15.3) years) were included. The main effects of EA and CBZ were significant (P < 0.001), and there was a significant interaction was identified between the interventions (P = 0.041). Participants who received EA (mean difference [MD], -0.3 [95% CI, -0.40 to -0.20] at week 2; -1.6 [-1.70 to -1.50] at week 4; -1.1 [-1.31 to -0.89] at week 16; -0.8 [-1.01 to -0.59] at week 28), CBZ (MD, -0.6 [95% CI, -0.70 to -0.50] at week 2; -0.9 [-1.03 to -0.77] at week 4, -0.2 [-0.41 to 0.01] at week 16, 0.2 [-0.01 to 0.41] at week 28), and the combination of both (MD, -1.8 [95% CI, -1.90 to -1.70] at week 2; -3.7 [-3.83 to -3.57] at week 4, -3.4 [-3.61 to -3.19] at week 16, -2.9 [-3.11 to -2.69] at week 28) had a greater reduction in VAS score over the treatment phase than their respective control groups (sham EA, placebo, and sham EA plus placebo). EA-related adverse events (6/59, 10.17%) were lower than that of CBZ (15/59, 25.42%) during the whole phases. CONCLUSIONS: EA or CBZ alone are effective treatments for TN, while the combination of EA and low-dosage CBZ exerts a greater benefit. These findings in this trial demonstrate that the combination of EA and low-dosage CBZ may be clinically effective under certain circumstances. TRIAL REGISTRATION: NCT03580317.