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1.
Phytomedicine ; 126: 155435, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38394727

RESUMO

BACKGROUND: Accumulating evidence indicates the crucial role of microglia-mediated inflammation and the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in the pathogenesis of Parkinson's disease (PD). Baohuoside I, a natural flavonoid extracted from Herba Epimedii, has been shown to possess anti-inflammatory effects, but its potential neuroprotective effects and mechanism against PD have not been documented. STUDY DESIGN AND METHODS: The anti-inflammatory effects of Baohuoside I were evaluated by LPS-induced BV2 cells or primary microglia isolated from wide type or G protein-coupled estrogen receptor (GPER) gene knockout mice. The underlying mechanism related to GPER-mediated NLRP3 inflammasome inhibition was further explored using LPS-induced GPER+/+ or GPER-/- mouse models of PD. The neuroprotective effects of Baohuoside I were detected through western blot analysis, real-time PCR, molecular docking, mouse behavioral tests, immunofluorescence, and immunohistochemistry. RESULTS: Baohuoside I significantly alleviated LPS-induced neuroinflammation by inhibiting the activation of NF-κB signal and the increase of pyroptosis levels as evidenced by the downregulated expression of pyroptosis-related proteins (NLRP3, ASC, pro-Caspase-1, IL-1ß) in microglia cells. Intragastric administration of Baohuoside I protected against LPS-induced motor dysfunction and loss of dopaminergic neurons, reduced pro-inflammatory cytokines expressions, and inhibited microglial (Iba-1) and astrocyte (GFAP) activation in the nigrostriatal pathway in LPS-induced mouse model of PD. Pretreatment with GPER antagonist G15 in microglia cells or GPER gene deletion in mice significantly blocked the inhibitory effects of Baohuoside I on LPS-induced neuroinflammation and activation of the NLRP3/ASC/Caspase-1 pathway. Molecular docking further indicated that Baohuoside I might bind to GPER directly with a binding energy of -10.4 kcal/mol. CONCLUSION: Baohuoside I provides neuroprotective effects against PD by inhibiting the activation of the NF-κB signal and NLRP3/ASC/Caspase-1 pathway. The molecular target for its anti-inflammatory effects is proved to be GPER in the PD mouse model. Baohuoside I may be a valuable anti-neuroinflammatory agent and a drug with well-defined target for the treatment of PD.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Camundongos , Animais , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Flavonoides/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Caspases/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Microglia , Camundongos Endogâmicos C57BL
2.
Travel Med Infect Dis ; 58: 102689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38295966

RESUMO

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.


Assuntos
Doença da Altitude , Edema Encefálico , Doenças Retinianas , Humanos , Altitude , Doença da Altitude/complicações , Doença da Altitude/diagnóstico , Doenças Retinianas/complicações , Hipóxia , Doença Aguda , Edema Encefálico/diagnóstico , Edema Encefálico/etiologia
3.
Phytomedicine ; 123: 155220, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056149

RESUMO

BACKGROUND: Resistance to chemotherapy in gastric cancer (GC) is a ubiquitous challenge for its treatment. Yi-qi-hua-yu-jie-du decoction (YJD), an empirical formula in Traditional Chinese Medicine (TCM), demonstrated survival-prolonging functions in patients with GC. Previous research has shown that YJD could also inhibit drug resistance in GC. However, the precise mechanisms for how YJD accomplishes this remain incompletely explained. PURPOSE: The research aimed to identify differential metabolic characteristics in cisplatin-resistant GC and investigate whether YJD can target these differences to suppress GC drug resistance. METHODS: Metabolomic analysis was conducted to identify metabolic disparities between cisplatin-resistant and parental GC cells, as well as metabolic modifications resulting from YJD intervention in cisplatin-resistant GC cells. The effect of YJD on ferroptosis stimulation was assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), iron ions, the reduced glutathione (GSH) to oxidised glutathione (GSSG) ratio, and alterations in mitochondrial morphology. Western blotting and quantitative real-time polymerase chain reaction (Q-PCR) were employed to verity the mechanisms of YJD-triggered ferroptosis through GPX4 and NRF2 overexpression models, alongside the AKT activator SC79. In vivo validation was conducted using nude mouse xenograft models. RESULTS: Cisplatin-resistant GC exhibited altered GSH/GPX4 metabolism, and ferroptosis was a significantly enriched cell death pattern with YJD treatment in cisplatin-resistant GC cells. Ferroptosis biomarkers, including ROS, MDA, iron ions, the GSH/GSSG ratio, and mitochondrial morphology, were remarkably changed with the YJD intervention. Mechanistic experiments demonstrated that YJD inhibited the phosphorylation cascade activity of the AKT/GSK3ß pathway, thereby reducing NRF2 expression. The level of GPX4, a crucial enzyme involved in glutathione metabolism, was attenuated, facilitating ferroptosis induction in cisplatin-resistant GC. CONCLUSION: The research reveals, for the first time, changes in GSH/GPX4 metabolism in cisplatin-resistant GC cells based on metabolomic analysis. YJD induced ferroptosis in cisplatin-resistant GC by inhibiting GPX4 through the AKT/GSK3ß/NRF2 pathway, thus attenuating the cisplatin drug resistance in GC. Our findings identify metabolic changes in cisplatin-resistant GC and establish a theoretical framework for YJD on tackling drug resistance in GC through ferroptosis.


Assuntos
Ferroptose , Neoplasias Gástricas , Animais , Camundongos , Humanos , Cisplatino/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas c-akt , Dissulfeto de Glutationa , Espécies Reativas de Oxigênio , Íons , Ferro
4.
J Tradit Complement Med ; 13(3): 245-262, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37128200

RESUMO

Background and aim: Gastric cancer (GC) is a common malignant tumor worldwide. Modified Gui-shao-liu-jun-zi decoction (mGSLJZ) is a clinically effective traditional Chinese medicine (TCM) compound in GC treatment. This study aimed to analyze main chemical substances of mGSLJZ and investigate active ingredients and molecular mechanism of mGSLJZ against GC. Experimental procedure: HPLC-Q-TOF-MS/MS was used to analyze chemical substances of mGSLJZ, and potential active ingredients were screened from TCMSP. The target set of mGSLJZ for GC was obtained based on SwissTargetPrediction. The PPI network was constructed to screen out core targets. GO and KEGG enrichment analyses were conducted to identify BPs, CCs, MFs and pathways. The "active ingredient-core target-pathway" regulatory network was constructed to obtain core substances. Subsequently, Oncomine, Proteinatlas and molecular docking were performed to validate these findings. The cell experiments were conducted to confirm the anti-GC effects of mGLSJZ. Results and conclusion: Forty-one potential active ingredients were filtered out from 120 chemical substances in mGSLJZ, including various organic acids and flavonoids. The top 10 key targets, 20 related pathways and 6 core medicinal substances were obtained based on network pharmacology analysis. Molecular docking results indicated that the core substances and key targets had good binding activities. The cell experiments validated that mGSLJZ and the core substances inhibited the proliferation in multiple GC cells and that mGLSJZ restrained the migration of GC. Meanwhile, the top 5 targets and top 2 pathways were verified. The rescue experiments demonstrated that mGSLJZ suppressed the proliferation and migration of GC through the PI3K/AKT/HIF-1 pathway.

6.
Zhongguo Zhong Yao Za Zhi ; 47(21): 5765-5774, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471994

RESUMO

Mineral medicine is a characteristic element of advantage of traditional Chinese medicine(TCM), which embodies unique scientific connotation. Cinnabaris is a characteristic drug in Chinese medicinal preparations, especially in Chinese medicinal pediatric preparations. Because of the adverse reactions caused by mercury contained, the safety and application of Cinnabaris have attracted much attention. To explore the application regularity and the value of the pediatric preparations containing Cinnabaris, this study statistically analyzed 32 Cinnabaris-contained pediatric preparations in the 2020 edition of the Chinese Pharmacopoeia and 105 pediatric preparations containing Cinnabaris in the Dictionary of Traditional Chinese Medicine Prescriptions(Vol. Ⅰ and Ⅱ). The statistical results indicated that the pediatric preparations and formulae containing Cinnabaris had great advantages in the treatment of pediatric convulsions, but there were still problems in dosage form, dosage, and quality control. In this study, ICP-MS and LC-AFS were further used to determine the content of total mercury and soluble mercury in 15 commercially available pediatric preparations containing Cinnabaris. It was found that the total mercury content was far higher than soluble mercury content in the sample preparations, and there was no obvious correlation between them. According to the results, the research and application strategies of Cinnabaris were put forward in order to provide references for the rational application of Cinnabaris in pediatric preparations.


Assuntos
Medicamentos de Ervas Chinesas , Mercúrio , Humanos , Criança , Medicina Tradicional Chinesa , Minerais , Controle de Qualidade
7.
Clin Nutr ; 41(12): 2651-2658, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36308984

RESUMO

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.


Assuntos
Óleos de Peixe , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Prospectivos , Predisposição Genética para Doença , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de Risco , Suplementos Nutricionais
8.
BMC Genomics ; 23(1): 655, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109727

RESUMO

BACKGROUND: As one of three essential nutrients, potassium is regarded as a main limiting factor for growth and development in plant. Sweet potato (Ipomoea batatas L.) is one of seven major food crops grown worldwide, and is both a nutrient-rich food and a bioenergy crop. It is a typical 'K-favoring' crop, and the level of potassium ion (K+) supplementation directly influences its production. However, little is known about the transcriptional changes in sweet potato genes under low-K+ conditions. Here, we analyzed the transcriptomic profiles of sweet potato roots in response to K+ deficiency to determine the effect of low-K+ stress on this economically important crop. RESULTS: The roots of sweet potato seedlings with or without K+ treatment were harvested and used for transcriptome analyses. The results showed 559 differently expressed genes (DEGs) in low and high K+ groups. Among the DEGs, 336 were upregulated and 223 were downregulated. These DEGs were involved in transcriptional regulation, calcium binding, redox-signaling, biosynthesis, transport, and metabolic process. Further analysis revealed previously unknow genes involved in low-K+ stress, which could be investigated further to improve low K+ tolerance in plants. Confirmation of RNA-sequencing results using qRT-PCR displayed a high level of consistency between the two experiments. Analysis showed that many auxin-, ethylene- and jasmonic acid-related genes respond to K+ deficiency, suggesting that these hormones have important roles in K+ nutrient signaling in sweet potato. CONCLUSIONS: According to the transcriptome data of sweet potato, various DEGs showed transcriptional changes in response to low-K+ stress. However, the expression level of some kinases, transporters, transcription factors (TFs), hormone-related genes, and plant defense-related genes changed significantly, suggesting that they have important roles during K+ deficiency. Thus, this study identifies potential genes for genetic improvement of responses to low-K+ stress and provides valuable insight into the molecular mechanisms regulating low K+ tolerance in sweet potato. Further research is required to clarify the function of these DEGs under low-K+ stress.


Assuntos
Ipomoea batatas , Deficiência de Potássio , Cálcio/metabolismo , Etilenos/metabolismo , Perfilação da Expressão Gênica , Hormônios/metabolismo , Ácidos Indolacéticos/metabolismo , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Potássio/metabolismo , Deficiência de Potássio/genética , RNA/metabolismo , Fatores de Transcrição/metabolismo
9.
Chin Med ; 17(1): 93, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35941687

RESUMO

BACKGROUND: The drug resistance of tumor stem cells is an obstacle in gastric cancer (GC) treatment and the high expression of ABC transporters is a classic reason for drug resistance. This study aimed to construct a reliable GC drug-resistant stem cell model and explore the inhibitory effect and mechanism of Yi-qi-hua-yu-jie-du medicated serum (YQHY) on the drug resistance of GC stem cells based on ABC transporters. METHODS: The tumor stemness biomarker CD44 was primary identification from WGCNA. The magnetic-activated cell sorting (MACS) method was used to separate CD44( +)BGC823/5-Fu (BGC823/5-Fu-CSCs) cells and the stemness characteristics were verified from multiple dimensions. Then, the drug resistance index and expression of ABC transporter genes MDR1 and MRP1 were detected in CD44(-)/CD44(+) cells. The inhibition and apoptosis rates of the cells administrated with YQHY or/and 5-Fu were calculated to confirm that YQHY can suppress the drug resistance of BGC823/5-Fu-CSCs. Afterwards, the effects of YQHY on the expression of MDR1 and MRP1 and the activation of the PI3K/Akt/Nrf2 pathway were observed. Finally, under the administration of IGF-1 (the activator of PI3K/Akt pathway) and Nrf2 siRNA, the mechanism of YQHY on reversing the drug resistance of BGC823/5-Fu-CSCs through inhibiting the expression of MDR1 and MRP1 via PI3K/Akt/Nrf2 was verified. RESULTS: CD44 was a reliable GC stemness biomarker and can be applied to construct the drug-resistant GC stem cell model CD44(+)BGC823/5-Fu. The growth rate, cell proliferation index, soft agar colony formation, expression of stemness specific genes and tumorigenesis ability of CD44(+)BGC823/5-Fu cells were significantly higher than those of CD44(-)BGC823/5-Fu cells. BGC823/5-Fu-CSCs exhibited strong drug resistance to 5-Fu and high expression of ABC transporter genes MDR1 and MRP1 compared to CD44(-) cells. YQHY increased the inhibition and apoptosis rates to efficiently inhibit the drug resistance of BGC823/5-Fu-CSCs. Meanwhile, it suppressed the expression of MDR1 and MRP1 and restrained the activation of PI3K/Akt/Nrf2 signaling pathway. Finally, it was found that IGF-1 partially restored the activation of PI3K/Akt/Nrf2 pathway, alleviated the inhibition of MDR1 and MRP1, blocked the proliferation-inhibitory and apoptosis-promotion effects. YQHY and si-Nrf2 synergistically suppressed the MDR1/MRP1 expression and the drug resistance of BGC823/5-Fu-CSCs. CONCLUSIONS: CD44 was a reliable GC stemness biomarker, and the high expression of ABC transporter genes MDR1 and MRP1 was an important feature of drug-resistant stem cells. YQHY inhibited the MDR1 and MRP1 expression via PI3K/Akt/Nrf2 pathway, thus reversing the drug resistance of BGC823/5-Fu-CSCs.

10.
Front Nutr ; 9: 930176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782942

RESUMO

The severity of coronavirus disease 2019 (COVID-19) is determined not only by viral damage to cells but also by the immune reaction in the host. In addition to therapeutic interventions that target the viral infection, immunoregulation may be helpful in the management of COVID-19. Vitamin D exerts effects on both innate and adaptive immunity and subsequently modulates immune responses to bacteria and viruses. Patients with chronic kidney disease (CKD) frequently have vitamin D deficiency and increased susceptibility to infection, suggesting a potential role of vitamin D in this vulnerable population. In this paper, we review the alterations of the immune system, the risk of COVID-19 infections and mechanisms of vitamin D action in the pathogenesis of COVID-19 in CKD patients. Previous studies have shown that vitamin D deficiency can affect the outcomes of COVID-19. Supplementing vitamin D during treatment may be protective against COVID-19. Future studies, including randomized control trials, are warranted to determine the effect of vitamin D supplementation on the recovery from COVID-19 in CKD patients.

11.
Altern Ther Health Med ; 28(8): 38-45, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35839116

RESUMO

Context: Orthopedic internal fixation implantation (OIFI) is a frequently adopted surgery for fractures, but it can trigger various adverse reactions and increase patients' risks of postoperative complications. Reducing those risks is paramount for obtaining better therapeutic effects for OIFI. Objective: The study intended to analyze the value of predictive nursing, based on healthcare failure modes and effects analysis (HFMEA), and combined with multimodal analgesia for improving postoperative rehabilitation after orthopedic internal fixation (OIFI), with the aim of offering reliable, accurate, and novel ideas and directions for future clinical OIFI and prognosis improvement for patients. Design: The research team designed a retrospective analysis. Setting: The study took place in the Department of the Operating Room at Hefei First People's Hospital in Hefei, Anhui, China. Participants: Participants were150 patients who needed OIFI at the hospital between January and December 2020. Intervention: Participants were assigned to one of two groups, 87 to the intervention group, who received treatment with HFMEA-based predictive care combined with multimodal analgesia after OIFI, and 63 to a control group who received routine nursing combined with multimodal analgesia after OIFI. Outcome Measures: Postintervention, the study measured the effective treatment rate, risk priority number (RPN)-the severity, possibility, and detectable degree of the risk, analgesic effects, self-controlled delivery times, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) levels, and incidence of adverse symptoms. Also postintervention, the participants completed a visual analogue scale (VAS) to indicate their satisfaction with the nursing as well as the Exercise of Self-care Agency (ESCA) scale and the Spielberger State-trait Anxiety Inventory (STAI). Results: The study found significant differences between the groups. The intervention group showed significantly lower RPN values, VAS scores for analgesia, TNF-α and IL-6 levels, and incidence of adverse symptoms and also indicated greater satisfaction with the nursing, a significantly higher ESCA score, and a significantly better psychological state. Conclusions: HFMEA-based predictive care combined with multimodal analgesia can substantially lower the risk and pain levels of patients undergoing OIFI and can improve their nursing experience and self-care ability, so it's worthy of clinical application, having great significance for patients' rehabilitation.


Assuntos
Analgesia Controlada pelo Paciente , Análise do Modo e do Efeito de Falhas na Assistência à Saúde , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/uso terapêutico , Interleucina-6
12.
Int J Mol Sci ; 23(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35806377

RESUMO

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.


Assuntos
Injúria Renal Aguda , Tratamento Farmacológico da COVID-19 , COVID-19 , Deficiência de Vitamina D , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , COVID-19/complicações , Cálcio , Humanos , SARS-CoV-2 , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
13.
Mitochondrial DNA B Resour ; 7(3): 507-509, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342793

RESUMO

Primulina tenuituba is a species in the Gesneriaceae family that is widely distributed in China. It is a karst-dwelling species with an enormous tolerance for extreme drought and high temperatures. The species is also used in traditional Chinese medicine. In this study, the complete chloroplast genome of P. tenuituba was assembled and characterized for the first time. The complete chloroplast genome exhibited a typical quadripartite cycle of 153,236 bp in length, including a pair of inverted repeats (IRs) of 25,494 bp, which were separated by a large single-copy (LSC) region of 84,364 bp and a small single copy (SSC) region of 17,884 bp. The GC content was 37.6%. The complete chloroplast genome of P. tenuituba contains 114 genes, including 80 protein-coding genes, 30 tRNAs genes, and four rRNAs. The phylogenetic analysis showed that P. tenuituba is closely related to P. eburnea. The newly reported chloroplast genome of P. tenuituba would provide valuable data for further studies on its evolution and adaptation mechanism.

14.
Acta Pharmacol Sin ; 43(1): 229-239, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33767381

RESUMO

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.


Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , DNA/antagonistas & inibidores , Descoberta de Drogas , Simulação de Acoplamento Molecular , Receptores Androgênicos/metabolismo , Antagonistas de Receptores de Andrógenos/química , Sítios de Ligação/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura Molecular , Receptores Androgênicos/química , Relação Estrutura-Atividade
15.
Biomed J ; 44(3): 293-303, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34119448

RESUMO

BACKGROUND: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM. METHODS: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay. RESULTS: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC50 of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir. CONCLUSION: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Perilla frutescens , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Inativação de Vírus , Animais , COVID-19 , Chlorocebus aethiops , Humanos , Perilla frutescens/química
16.
Int Clin Psychopharmacol ; 36(4): 208-213, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34030167

RESUMO

Pharmacological intervention played an important role in the management of tic disorder. Large-scale prescription data for pediatric tic disorder patients in the real-world setting were scarce. The demographic and prescription data of tic disorder were extracted from the electronic medical records database of Beijing Children's Hospital from 2018 to 2020. The intervention choice for outpatient pediatric tic disorder patients was analyzed. A total of 20 417 patients were included, 28.1% (n = 5028) of them did not receive any pharmacological treatment. Over 70% were prescribed with anti-tic medication. For children less than 6 years of age, clonidine adhesive patches (CAPs) and traditional Chinese medicine (TCM) were the common choice. With the age growing, the use of antipsychotics was on the rise; 22% (n = 3389) were prescribed for at least two anti-tic medication, and the most common medication combination group was tiapride and TCM (33.7%), followed by CAP and TCM (22.1%). The clinical intervention choice for tic disorder is highly individualized. The pharmacological choice was influenced by severity, duration of symptom, age, the acceptance of parents and other factors.


Assuntos
Transtornos de Tique , Criança , China , Registros Eletrônicos de Saúde , Hospitais Pediátricos , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária , Transtornos de Tique/tratamento farmacológico
17.
Taiwan J Obstet Gynecol ; 60(2): 363-366, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33678344

RESUMO

OBJECTIVE: To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer. CASE REPORT: There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab. CONCLUSIONS: PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/secundário , Neoplasias Colorretais/terapia , Cistadenocarcinoma Seroso/secundário , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução , Diagnóstico Diferencial , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/terapia , Humanos , Pessoa de Meia-Idade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia
18.
Clin Case Rep ; 9(3): 1283-1287, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33768827

RESUMO

Abnormal acid-base status (metabolic acidosis or alkalosis), inappropriate urine electrolytes excretion (high or low Na+ and Cl-), and higher required dose of potassium supplement (4-5 mmol/kg) are suggestive of non-TPP causes of hypokalemia.

19.
Sci Rep ; 11(1): 1905, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479376

RESUMO

Sparganii rhizoma (SL) has potential therapeutic effects on gastric cancer (GC), but its main active ingredients and possible anticancer mechanism are still unclear. In this study, we used HPLC-Q-TOF-MS/MS to comprehensively analyse the chemical components of the aqueous extract of SL. On this basis, a network pharmacology method incorporating target prediction, gene function annotation, and molecular docking was performed to analyse the identified compounds, thereby determining the main active ingredients and hub genes of SL in the treatment of GC. Finally, the mRNA and protein expression levels of the hub genes of GC patients were further analysed by the Oncomine, GEPIA, and HPA databases. A total of 41 compounds were identified from the aqueous extract of SL. Through network analysis, we identified seven main active ingredients and ten hub genes: acacetin, sanleng acid, ferulic acid, methyl 3,6-dihydroxy-2-[(2-hydroxyphenyl) ethynyl]benzoate, caffeic acid, adenine nucleoside, azelaic acid and PIK3R1, PIK3CA, SRC, MAPK1, AKT1, HSP90AA1, HRAS, STAT3, FYN, and RHOA. The results indicated that SL might play a role in GC treatment by controlling the PI3K-Akt and other signalling pathways to regulate biological processes such as proliferation, apoptosis, migration, and angiogenesis in tumour cells. In conclusion, this study used HPLC-Q-TOF-MS/MS combined with a network pharmacology approach to provide an essential reference for identifying the chemical components of SL and its mechanism of action in the treatment of GC.


Assuntos
Curcuma/química , Medicamentos de Ervas Chinesas/química , Rizoma/química , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinases/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Espectrometria de Massas em Tandem
20.
Cancer Manag Res ; 12: 12385-12394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33293864

RESUMO

Chemotherapy is the main clinical treatment method of gastric cancer. Multidrug resistance (MDR) has become a common phenomenon with the development of tumors, which alleviates the effect of chemotherapy and makes it difficult to break the bottleneck of survival rate of advanced gastric cancer. Therefore, the exploration of MDR reversal agents for gastric cancer is the focus and also the difficulty of current treatment. Currently, the researches on the mechanisms of drug resistance in gastric cancer have been continuously deepened, which reveal different pathways and targets of MDR, laying a solid foundation for studying reversal agents. As a kind of natural medicine, traditional Chinese medicine (TCM) owns the characteristics of low toxicity, high safety and effectiveness. It can inhibit the occurrence, growth and metastasis of tumors, and reverse MDR via multiple pathways and mechanisms, the pathological function of which has become a research hotspot in recent years. TCM reversers are mainly divided into Chinese medicine monomers, Chinese patent medicines, and Chinese herbal compounds. With certain quantity and advantage, TCM reversers for MDR play an important role in the clinical treatment and show great potential in gastric cancer.

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