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1.
Front Nutr ; 9: 754707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571897

RESUMO

Carotenoids protect organs, tissues, and cells from the damaging action of singlet oxygen, oxygen radicals, and lipid peroxides. This systematic review was sought to evaluate the influence of oral carotenoids on antioxidant/oxidative markers, blood carotenoids levels, and lipid/lipoprotein parameters in human subjects. A comprehensive review of relevant literature was conducted in PubMed, Web of Sciences, and the Cochrane library, from 2000 to December 2020. Randomized controlled trials, case-controlled trials, or controlled trials were identified. A total of eighteen trials were included, with the target populations being healthy subjects in 16 studies, athletes in 1 study, and pregnant women in 1 study. The meta-analysis results showed that carotenoids complex supplementation significantly increased the levels of antioxidative parameters ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) [standardized mean difference (SMD) = 0.468; 95% CI: 0.159-0.776, p = 0.003; SMD = 0.568; 95% CI: 0.190-0.947, p = 0.003] and decreased the blood triglyceride (TG) level (SMD = -0.410, 95% CI: -0.698 to -0.122, p = 0.005). Oral carotenoids supplement significantly increased the blood levels of ß-carotene (SMD = 0.490, 95% CI: 0.123-0.858, p = 0.009), α-tocopherol (SMD = 0.752, 95%CI: 0.020-1.485, p = 0.044), and the intaking durations were 8 weeks. The levels of antioxidative enzymes and other lipid/lipoprotein parameters were not different between subjects receiving carotenoids and controls (p > 0.05). In conclusion, our systematic review showed that the carotenoids complex is beneficial for alleviating potential oxidative stress via interacting with free radicals or decreasing blood TG levels. The intaking duration of carotenoids should be 8 weeks to reach enough concentration for function.

2.
Exp Dermatol ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35441732

RESUMO

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2-like type of gene expression in BMDMs with the inhibited Il-6, Il1-ß and Arg-1 and induced Tnf-α, Il-10 and Mgl-1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN. We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis-induced skin lesions were accompanied with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c-JUN pathway, effects that can then control the expression of inflammatory factors.

3.
Dermatol Ther (Heidelb) ; 12(4): 933-947, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35313362

RESUMO

INTRODUCTION: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease with rising prevalence. Topical corticosteroids (TCS) are recommended as first-line therapy for patients with AD in China; however, corticophobia is a widespread concern, which can manifest as noncompliance: in a previous Chinese study, almost all parents whose children had AD were very concerned about the side effects of TCS and, as a result, nearly half did not use it in the event of recurrence. We propose a TCS-sparing treatment algorithm for the management of infants, children, adolescents, and adults with mild-to-moderate AD, to guide clinical practice in China. METHODS: A panel of eight experts in AD from China and one expert from Germany formed to develop a practical algorithm for the management of mild-to-moderate AD, focusing on pimecrolimus. RESULTS: Irrespective of body location, all patients with mild AD (including acute flares) and infants with moderate AD should apply the topical calcineurin inhibitor (TCI) pimecrolimus twice daily to the affected area until symptoms disappear. For children, adolescents, and adults with moderate AD, pimecrolimus should be applied twice daily to sensitive skin areas, and a TCI (either pimecrolimus or tacrolimus) should be applied twice daily to other body locations. Short-term administration of TCS, followed by TCI twice daily, is recommended for most patients with moderate AD experiencing acute flares, regardless of lesion site. Emollients should be used regularly. CONCLUSIONS: The algorithm presented intends to simplify treatment of AD in China and guide clinical decision-making.

4.
Redox Biol ; 51: 102262, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35180475

RESUMO

The term ferroptosis coined in 2012 causes acute kidney injury (AKI). However, its pathway mechanism in AKI is poorly understood. In this study, we conducted an RNA-sequence analysis of kidneys in AKI and normal mice to explore the pathway mechanism of ferroptosis. Consequently, differentially expressed genes highlighted Acyl-CoA synthetase long-chain family (ACSL4), a known promotor for ferroptosis. Besides, RT-PCR, Western blot, and immunohistochemical analyses confirmed its upregulation. HIF-1α was downregulated in I/R-AKI mice, and in vitro studies confirmed a negative regulation of HIF-1α on ACSL4. To explore the role of ACSL4 in AKI, we constructed ACSL4 knockout in kidney tubules of mice-as Cdh16Cre-ACSL4F/F mice. Results revealed that ACSL4 knockout significantly reduced ferroptosis and inhibited the functional and pathological injury of AKI mice. Meanwhile, the kidneys of Cdh16Cre-ACSL4F/F mice demonstrated a significantly decreased inflammation and macrophage infiltration. Further, additional explorations were explored to decipher a more thorough understanding of ferroptotic immunogenicity. As a result, neutrophils were not directly recruited by ferroptotic cells, but by ferroptotic cell-induced macrophages. Further, ACSL4 inhibitor rosiglitazone significantly inhibited AKI. Collectively, these data provide novel insights into the AKI pathogenesis, and defined ACSL4 as an effective target in AKI.


Assuntos
Injúria Renal Aguda , Ferroptose , Injúria Renal Aguda/metabolismo , Animais , Coenzima A Ligases/genética , Feminino , Ferroptose/genética , Humanos , Masculino , Camundongos , Rosiglitazona/farmacologia
5.
Dermatol Ther ; 35(5): e15403, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35201628

RESUMO

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.


Assuntos
Hipertermia Induzida , Verrugas , Crioterapia/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Nitrogênio , Resultado do Tratamento , Verrugas/terapia
6.
BMC Infect Dis ; 22(1): 150, 2022 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-35152879

RESUMO

BACKGROUND: Invasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited. METHODS: We included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3). RESULTS: Of the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25-74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level. CONCLUSION: Our results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level.


Assuntos
Candidíase Invasiva , Sepse , Idoso , Bactérias , Humanos , Unidades de Terapia Intensiva , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
7.
Acta Derm Venereol ; 102: adv00655, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35083495

RESUMO

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.


Assuntos
Hipertermia Induzida , Verrugas , Crioterapia/efeitos adversos , Humanos , Hipertermia Induzida/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Verrugas/tratamento farmacológico
8.
J Am Acad Dermatol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026342

RESUMO

BACKGROUND: Vunakizumab (SHR-1314) is a novel interleukin 17A monoclonal antibody that has shown preliminary efficacy and tolerability in phase I trials. OBJECTIVE: To evaluate the efficacy and safety of vunakizumab in moderate-to-severe plaque psoriasis. METHODS: In this 36-week, multicenter, double-blinded, phase II study (NCT03463187), 187 eligible patients with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive vunakizumab (40, 80, 160, or 240 mg) or placebo subcutaneously, every 4 weeks, until week 12 (2 more drug administrations for the vunakizumab groups on weeks 16 and 20). The primary end point was at least 75% improvement in the Psoriasis Area and Severity Index at week 12. RESULTS: At week 12, there were significantly greater proportions of responders with at least 75% improvement in the Psoriasis Area and Severity Index in all vunakizumab groups compared to placebo (40, 80, 160, and 240 mg: 56.8%, 65.8%, 81.6%, and 86.5%, respectively, vs 5.4%; P < .001 for all); the proportions of patients achieving Physician's Global Assessment responses of 0 or 1 were also higher with vunakizumab (45.9%, 47.4%, 60.5%, and 73.0%, respectively, vs 8.1%). No unexpected adverse effects were observed. LIMITATIONS: The study was relatively short in duration and included no active control. CONCLUSION: Vunakizumab showed promising efficacy for moderate-to-severe plaque psoriasis, with good tolerability, warranting further investigation in larger and longer-term studies.

9.
Allergy Asthma Immunol Res ; 14(1): 131-142, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34983113

RESUMO

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

10.
Adv Ther ; 39(1): 583-597, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34816373

RESUMO

INTRODUCTION: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated. RESULTS: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups. CONCLUSION: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).


Plaque psoriasis is a chronic, autoimmune, inflammatory skin disease associated with significant morbidity and reduced quality of life. In China, the prevalence of plaque psoriasis increased four-fold between 1987 and 2012. Adalimumab is a biologic antibody used to treat plaque psoriasis globally. However, high treatment costs remain as a significant barrier to adalimumab therapy. Therefore, HLX03 has been developed as an adalimumab (Humira®) biosimilar, which is almost identical to the licensed reference adalimumab, but less expensive and more accessible to patients. In this randomized clinical trial, the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response which would affect its efficacy and safety) of HLX03 were compared with the reference adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. Efficacy was evaluated by comparing the changes in severity and extent of disease using Psoriasis Area and Severity Index score between treatment initiation and week 16. Safety was monitored by adverse events, laboratory tests and vital signs. Immunogenicity was assessed by the incidence of antidrug antibodies. Among the 262 randomized patients, 131 received HLX03 and 130 received adalimumab. Both groups reported similar improvements in Psoriasis Area and Severity Index scores (between-group difference fell within the prespecified equivalence margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety and immunogenicity profiles. In summary, HLX03 demonstrated equivalent efficacy to adalimumab, validating it as an alternative treatment for patients with plaque psoriasis in China.


Assuntos
Medicamentos Biossimilares , Psoríase , Adalimumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Pain ; 163(4): 652-664, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252911

RESUMO

ABSTRACT: Group I metabotropic glutamate receptors (group I mGluRs) have been implicated in several central nervous system diseases including chronic pain. It is known that activation of group I mGluRs results in the production of inositol triphosphate (IP3) and diacylglycerol that leads to activation of extracellular signal-regulated kinases (ERKs) and an increase in neuronal excitability, but how group I mGluRs mediate this process remains unclear. We previously reported that Orai1 is responsible for store-operated calcium entry and plays a key role in central sensitization. However, how Orai1 is activated under physiological conditions is unknown. Here, we tested the hypothesis that group I mGluRs recruit Orai1 as part of its downstream signaling pathway in dorsal horn neurons. We demonstrate that neurotransmitter glutamate induces STIM1 puncta formation, which is not mediated by N-Methyl-D-aspartate (NMDA) or α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Glutamate-induced Ca2+ entry in the presence of NMDA or AMPA receptor antagonists is eliminated in Orai1-deficient neurons. Dihydroxyphenylglycine (DHPG) (an agonist of group I mGluRs)-induced Ca2+ entry is abolished by Orai1 deficiency, but not affected by knocking down of transient receptor potential cation channel 1 (TRPC1) or TRPC3. Dihydroxyphenylglycine-induced activation of ERKs and modulation of neuronal excitability are abolished in cultured Orai1-deficient neurons. Moreover, DHPG-induced nociceptive behavior is markedly reduced in Orai1-deficient mice. Our findings reveal previously unknown functional coupling between Orai1 and group I mGluRs and shed light on the mechanism underlying group I mGluRs-mediated neuronal plasticity.


Assuntos
N-Metilaspartato , Receptores de Glutamato Metabotrópico , Animais , Cálcio/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacologia , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Células do Corno Posterior/metabolismo , Receptores de AMPA/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais
12.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34751412

RESUMO

Vitiligo is a depigmentation disease commonly seen in clinical practice, mainly involving loss of functional epidermal pigment cells and hair follicle melanocytes. Narrow­band ultraviolet B (NB­UVB) has emerged as the first choice of treatment for vitiligo, but long­term exposure may have serious consequences. Recently, it was reported that adipose­derived stem cells (ADSCs) improve melanocyte growth and the efficacy of melanocyte transplantation. The present study aimed to examine the efficacy of NB­UVB/ADSC­transplantation combined therapy on a mouse vitiligo model and explore the underlying mechanisms by focusing on endoplasmic reticulum stress and cellular calcium (Ca2+) homeostasis. Vitiligo mice models were established by applying 40% monobenzone (MBZ) cream twice daily and treated with NB­UVB/ADSC combination therapy. Some treated mice were also given ML385, a nuclear factor erythroid 2 like 2 (Nr2) inhibitor. Histopathological changes were evaluated using a depigmentation evaluation score and observed with hematoxylin and eosin staining on skin tissues. ELISA was used to measure diagnostic markers in plasma. Flow cytometric assay was performed to quantify CD3+, CD4+ and CD8+ levels. Expression levels of associated proteins were detected with western blot and immunofluorescence. Treatment of mice with MBZ­induced depigmentation patches on the skin was accompanied with loss of redox balance and disruption of cellular Ca2+ homeostasis. Oxidative stress and Ca2+ unbalancing were improved after the mice were treated by NB­UVB/ADSCs transplantation combination therapy. ML385, strongly negated the protective effect of NB­UVB/ADSC transplantation combination therapy, indicating the critical role of Nr2 signaling. The findings improved the understanding of the pathogenesis of vitiligo and will guide future development of therapeutic strategies against it.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Pigmentação da Pele/fisiologia , Vitiligo/terapia , Animais , Cálcio/metabolismo , China , Estresse do Retículo Endoplasmático/fisiologia , Epiderme/metabolismo , Feminino , Folículo Piloso/metabolismo , Homeostase , Hidroquinonas/efeitos adversos , Hidroquinonas/farmacologia , Melanócitos/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/fisiologia , Estresse Oxidativo , Pele/patologia , Pigmentação da Pele/genética , Raios Ultravioleta , Terapia Ultravioleta/métodos , Vitiligo/metabolismo , Vitiligo/fisiopatologia
13.
Oncol Rep ; 47(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34935059

RESUMO

Although gemcitabine (GEM) has been used to treat bladder cancer (BC) for a number of years, severe adverse events or drug resistance frequently develops. A series of drugs have been proved to sensitize patients to GEM and reduce the side effects. The aim of the present study was to evaluate the potential effects of berberine (BER) on GEM­induced cytotoxicity in BC and to explore the possible underlying mechanisms. T24 and 5637 human BC cell lines were treated with GEM and/or BER before cell proliferation, apoptosis and migration were studied. Oncomine databases and Gene Expression Profiling Interactive Analysis (GEPIA) were used to retrieve RAD51 recombinase (Rad51) mRNA expression. Overexpression plasmid or specific Rad51 small interfering RNA were used to examine the role of Rad51 in drug­treated BC cells. BC model mice were administered with GEM and/or BER before changes in tumor volume, size and Ki67 expression were assessed. BER enhanced GEM­induced cytotoxicity, apoptosis and inhibition of migration, whilst attenuating the GEM­induced upregulation of phosphorylated Akt and Rad51 expression. According to Oncomine and GEPIA analyses, Rad51 was found to be significantly upregulated in BC tissues compared with that in normal tissues, where there was a weak positive correlation between Rad51 and Akt1 expression. Knockdown of Rad51 enhanced GEM­induced cytotoxicity, whilst overexpression of Rad51 reversed the suppressed cell viability induced by BER and GEM. Inactivation of the PI3K/Akt pathway by LY294002 or BER enhanced GEM­induced cytotoxicity and downregulated Rad51 expression, whilst overexpression of constitutively active Akt restored Rad51 expression and cell viability that was previously decreased by BER and GEM. BER additively inhibited tumor growth and Ki67 expression when combined with GEM in vivo. These results suggest that BER can enhance GEM­induced cytotoxicity in BC by downregulating Rad51 expression through inactivating the PI3K/Akt pathway, which may represent a novel therapeutic target for BC treatment.


Assuntos
Berberina/farmacologia , Desoxicitidina/análogos & derivados , Sinergismo Farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rad51 Recombinase/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Transporte , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Regulação para Cima , Neoplasias da Bexiga Urinária/genética
15.
Am J Chin Med ; 49(8): 1871-1895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34961421

RESUMO

Shikonin is one of the primary active components extracted from the dried root ofZicao (Lithospermum erythrorhizon, Onosma paniculata, or Arnebia euchroma), a traditional Chinese herbal medicine. Shikonin is known to not only exert anti-proliferative, anti-inflammatory, and anti-angiogenic activities, but also play a crucial role in triggering the production of reactive oxygen species, suppressing the release of exosomes, and inducing apoptosis. Increasing evidence suggests that shikonin has a protective effect against skin diseases, including psoriasis, melanoma, and hypertrophic scars. In order to evaluate the application potential of shikonin in the treatment of skin diseases, this review is the first of its kind to provide comprehensive and up-to-date information regarding the uses of shikonin and its derivatives on skin diseases and its underlying mechanisms. In this review, we have focused on the signaling pathways and cellular targets involved in the anti-dermatosis effects of shikonin to bridge the gaps in the literature, thereby providing scientific support for the research and development of new drugs from a traditional medicinal plant.


Assuntos
Lithospermum , Naftoquinonas , Dermatopatias , Humanos , Inflamação , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Dermatopatias/tratamento farmacológico
16.
World Allergy Organ J ; 14(11): 100610, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34934470

RESUMO

Chronic urticaria (CU) is a debilitating skin disease that lasts for more than 6 weeks with wheals and/or angioedema, including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). In China, the prevalence of this disease is high, more than 1%, and on the rise. CU has a major impact on the quality of life (QoL) of patients who frequently experience sleep disturbance, depression, and anxiety. Nearly one-third of patients with CSU, in China, are resistant to second-generation H1-antihistamines (sgAHs), even at a fourfold dose (second line; off-label). Omalizumab is approved for the treatment of CSU treatment in Europe and shows remarkable efficacy and safety. In China, regulatory approval for the use of omalizumab is pending, and its use in clinical practice varies widely. Consensus on omalizumab CU treatment in China is urgently needed. The aim of this article is to propose a practical omalizumab treatment algorithm for the management of antihistamine-resistant CSU and CIndU in adults and special population including children and adolescents, and pregnant or breast feeding women, to guide daily clinical practice in China. In the development of this consensus, an expert group including mainly dermatologists, allergists, but also pulmonologists, ENTs, immunologists, and pediatricians in Allergic Disease Prevention and Control Committee, Chinese Preventive Medicine Association, reviewed the existing evidence and developed consensus on the use of omalizumab in CU patients from China. The goal of this consensus is to assist clinicians in making rational decisions in the management of refractory CU with omalizumab. The key clinical questions covered by the treatment algorithm are: 1) Omalizumab treatment routine strategy in both CSU and CIndU patients; 2) Recommended dose and treatment duration for different age stratification; 3) Treatment duration for CU patients with other allergic comorbidities; 4) Recommendation on omalizumab stopping strategy.

17.
Biosensors (Basel) ; 11(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34677355

RESUMO

In this study, we designed and manufactured a series of different microstructure topographical cues for inducing neuronal differentiation of cells in vitro, with different topography, sizes, and structural complexities. We cultured PC12 cells in these microstructure cues and then induced neural differentiation using nerve growth factor (NGF). The pheochromocytoma cell line PC12 is a validated neuronal cell model that is widely used to study neuronal differentiation. Relevant markers of neural differentiation and cytoskeletal F-actin were characterized. Cellular immunofluorescence detection and axon length analysis showed that the differentiation of PC12 cells was significantly different under different isotropic and anisotropic topographic cues. The expression differences of the growth cone marker growth-associated protein 43 (GAP-43) and sympathetic nerve marker tyrosine hydroxylase (TH) genes were also studied in different topographic cues. Our results revealed that the physical environment has an important influence on the differentiation of neuronal cells, and 3D constraints could be used to guide axon extension. In addition, the neurotoxin 6-hydroxydopamine (6-OHDA) was used to detect the differentiation and injury of PC12 cells under different topographic cues. Finally, we discussed the feasibility of combining the topographic cues and the microfluidic chip for neural differentiation research.


Assuntos
Diferenciação Celular , Sinais (Psicologia) , Neurônios , Animais , Células PC12 , Ratos
18.
Therapie ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34689959

RESUMO

BACKGROUND: We conducted this systematic review to clarify the efficacy and safety of benvitimod on psoriasis. METHODS: We searched the databases of PubMed, China National Knowledge infrastructure, Cochrane Library, Embase, Web of science to identify randomized controlled trials (RCTs) of benvitimod on psoriasis up to April 2021. RESULTS: Five RCTs of benvitimod on psoriasis were included. A total of 1237 patients were included. 0.5% or 1.0% benvitimod was applied topically once or twice a day. More patients in benvitimod group achieved PASI 90, PASI 75, PASI 50 and BSA reduction than placebo at Week 12. More patients in benvitimod group achieved PGA 0 or 1 than placebo since Week 6. There were no statistical significances in efficacies of benvitimod at different concentrations and frequencies. CONCLUSIONS: Benvitimod was effective and safe for psoriasis. More RCTs with high qualities are needed to further verify the current conclusion.

19.
J Cosmet Dermatol ; 20(12): 3880-3888, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34719113

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of resveratrol combined with ablative fractional CO2  laser system (AFL) treating skin photoaging. METHODS: Thirty-two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period. RESULTS: All subjects in TG achieved improvements of their photoaging signs compared to pre-treatment both the laser side and the non-laser side at 6 months (p < 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p < 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p < 0.05). On the non-laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p < 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG. CONCLUSION: The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.


Assuntos
Lasers de Gás , Envelhecimento da Pele , Dióxido de Carbono , Eritema/etiologia , Humanos , Lasers de Gás/efeitos adversos , Resveratrol/uso terapêutico , Resultado do Tratamento
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