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Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.
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Actinomadura , Antineoplásicos , Humanos , Estrutura Molecular , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , AntraquinonasRESUMO
BACKGROUND: Recent studies have demonstrated that copper (Cu) plays an important role in the progression of tumor diseases. Metastasis associated with colon cancer protein 1 (MACC1) promotes the transcription and expression of various tumor-related genes. Cytochrome c oxidase (COX) 19, present in the cytoplasm and intermembrane space of mitochondria, may transport Cu within the mitochondria. However, the mechanism through which MACC1 regulates the Cu homeostasis mediated by COX19 remains unclear. OBJECTIVES: The aim of this study was to elucidate the mechanism through which MACC1 initiates the transcription and expression of COX19, and promotes malignant behavior in tumor cells. METHODS: Immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) analyses were conducted to analyze the expression of MACC1 and COX19 proteins and genes in tumor and normal tissues. RNA-chromatin immunoprecipitation was used to detect the transcriptional initiation of COX19 by MACC1. The effects of MACC1 and COX19 on mitochondrial activity were determined using an ATP assay kit and Cytochrome c Oxidase Assay Kit. A Cell Counting Kit-8 kit was used to detect the effect of high-dose Cu or overexpression of MACC1 and COX19 on tumor cell proliferation. A xenograft mouse model was used to analyze the effect of the COX19 overexpression on the malignant behavior of the tumors. RESULTS: Cu enhanced the proliferation, invasion, and migration and inhibited apoptosis of SW480 cells. MACC1 was highly expressed in colorectal cancer tissues and activated the expression of COX19 by binding to its promoter region of COX19. The overexpression of COX19 increased mitochondrial Cu content and enhanced the activity of mitochondrial COX and ATP content, and inhibited apoptosis, promoted tumor growth of mice. CONCLUSIONS: Our results indicate that COX19 functions as a target gene of MACC1 and regulates mitochondrial activity and promotes the progression of colorectal cancer. MACC1/COX19 may provide a novel therapeutic target for colorectal cancer.
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Neoplasias do Colo , Neoplasias Colorretais , Animais , Humanos , Camundongos , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Cobre/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/metabolismo , Transativadores/genética , Transativadores/metabolismoRESUMO
Percutaneous nephrolithotomy is generally performed under general or regional anesthesia; however, it is rarely performed under local infiltration anesthesia (LIA). This study aimed to assess the safety and effectiveness of Chinese mini percutaneous nephrolithotomy (MPCNL) for upper urinary calculi under LIA. A retrospective analysis of 52 patients with upper urinary stones who underwent MPCNL under LIA from April 2019 to May 2022 was performed. Pethidine and Phenergan were intramuscularly injected 30 minutes preoperatively. Oxybuprocaine hydrochloride gel was applied to the urethra for lubricating and mucosal anesthesia. Ropivacaine hydrochloride and lidocaine were injected into the whole percutaneous channel for local anesthesia. An 8/9.8F ureteroscope and an 18F vacuum-assisted access sheath were applied in MPCNL. All 52 patients tolerated procedures and underwent operations successfully; none of them converted the anesthesia method or required additional analgesia. The mean visual analogue scale scores intraoperatively and at 6 hours, 24 hours, and 48 hours after surgery were 3.25 ± 0.52, 3.13 ± 0.69, 2.25 ± 0.56, and 1.58 ± 0.50, respectively. The stone free rate was 84.6%. Complications were seen in 6 (11.5%) patients, including fever in 2 patients (Clavien I), renal colic in 1 patient (Clavien I), clinically insignificant bleeding in 2 patients (Clavien I), and urinary tract infection in 1 patient (Clavien II). No severe complications were observed in any patients. Chinese MPCNL under LIA was a feasible option and achieved good outcomes in appropriately selected patients, and it may become the routine procedure for general patients.
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Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Cálculos Urinários , Humanos , Anestesia Local/métodos , População do Leste Asiático , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Nefrostomia Percutânea/métodos , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Urinários/cirurgiaRESUMO
BACKGROUND: Although depression has been a serious neuropsychiatric disorder worldwide, current antidepressants used in clinical practice have various weaknesses, including delayed onset and low rates of efficacy. Recently, the development of new antidepressants from natural herbal medicine has become one of the important research hotspots. Cucurbitacin B is a natural compound widely distributed in the Cucurbitaceae and Cruciferae families and has many pharmacological activities. The present study aimed to investigate whether cucurbitacin B possess antidepressant-like effects in mice. METHODS: The antidepressant-like effects of cucurbitacin B on mice behaviors were explored using the forced swim test, tail suspension test, open field test, sucrose preference test, and a chronic unpredictable mild stress model of depression together. Then, western blotting and immunofluorescence were used to examine the effects of cucurbitacin B on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling cascade and neurogenesis in the hippocampus of mice. Furthermore, BDNF-short hairpin RNA, K252a, and p-chlorophenylalanine methyl ester were adopted together to determine the antidepressant mechanism of cucurbitacin B. RESULTS: It was found that administration of cucurbitacin B indeed produced notable antidepressant-like effects in mice, which were accompanied with significant promotion in both the hippocampal BDNF-TrkB pathway and neurogenesis. The antidepressant mechanism of cucurbitacin B involves the hippocampal BDNF-TrkB system but not the serotonin system. CONCLUSIONS: Cucurbitacin B has the potential to be a novel antidepressant candidate.
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Antidepressivos , Fator Neurotrófico Derivado do Encéfalo , Depressão , Animais , Humanos , Camundongos , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismoRESUMO
Objective: The objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects. Data sources: We searched 6 online-databases (Jul-Dec 2022) using terms: "mental practice," "motor imagery training," "motor imagery practice," "mental training," "movement imagery," "cognitive training," "bilateral transfer," "interlimb transfer," "cross education," "motor learning," "strength," "force" and "motor performance." Study selection and data extraction: We selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis. Data synthesis: The meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT). Results: MIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57-0.98). The effect of MIT on BT was similar to that of PT (ES = -0.02, 95% CI = -0.15-0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57-2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74-1.17), and mixed-task (ES = 1.68, 95% CI = 1.26-2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14-0.78) and normal-task (ES = 0.56, 95% CI = 0.23-0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37-0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59-1.15). Conclusion: This review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors.
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OBJECTIVE: Local combined systemic therapy has been an important method for the treatment of unresectable hepatocellular carcinoma (HCC).The purpose of this study was to compare the effectiveness and safety of transarterial chemoembolization (TACE) plus Sorafenib versus TACE plus Apatinib for treating patients with unresectable HCC. METHODS: The clinical data of patients with unresectable HCC who were treated with TACE plus Sorafenib or TACE plus Apatinib at 5 Chinese medical centers between January 2016 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) was applied to reduce the bias from confounding factors. RESULTS: A total of 380 patients were enrolled, of whom 129 cases were treated with TACE plus Sorafenib and 251 cases with TACE plus Apatinib. After the 1:1 PSM, 116 pairs of patients were involved in this study. The results showed that the PFS and OS in the TACE-Sorafenib group were significantly longer than those in the TACE-Apatinib group (PFS: 16.79 ± 6.45 vs. 14.76 ± 6.98 months, P = 0.049; OS: 20.66 ± 6.98 vs. 17.69 ± 6.72 months, P = 0.013). However, the ORR in the TACE-Apatinib group was markedly higher than that in the TACE-Sorafenib group (70.69% vs. 56.03%, P = 0.021). There were more patients with adverse events (AEs) in the TACE-Apatinib group than those in the TACE-Sorafenib group before dose adjustment (87 vs. 63, P = 0.001); however, the number of patients who suffered from AEs was not significantly different between the two groups after the dose adjustment (62 vs. 55, P = 0.148). No treatment-related death was found in the two groups. Subgroup analysis revealed that patients with unresectable HCC could better benefit from regular doses than reduced doses (Sorafenib, 22.59 vs. 18.02, P < 0.001; Apatinib, 19.75 vs. 16.86, P = 0.005). CONCLUSION: TACE plus either Sorafenib or Apatinib could effectively treat patients with unresectable HCC, the safety of TACE plus Sorafenib was better. and the ORR of TACE plus Apatinib was higher.
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Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Antineoplásicos/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Terapia CombinadaRESUMO
Intrahepatic cholangiocarcinoma (ICC) is a rare, highly fatal hepatobiliary malignancy, with very limited treatment options and, consequently, a poor prognosis. Recently, emerging evidence has suggested the potential of quercetin (QE) for use in cancer therapy. The purpose of this study is to investigate whether QE could inhibit ICC. The effects of QE on the proliferation, apoptosis, and invasion of ICC were analyzed in vitro. The inhibitory effect of QE on ICC was also verified in vivo. The RNA sequence was applied to explore the mechanism of QE. Functional verification was also performed after RNA sequencing using activators and inhibitors of nuclear factor-kappa-B (NF-[Formula: see text]B) and ferroptosis. The results showed that QE could inhibit the proliferation and survival of ICC cells, induce the arrest of ICC cells in the G1 phase, promote the apoptosis of ICC cells, and inhibit the invasion of ICC cells. Furthermore, QE could promote ferroptosis in ICC cells by inhibiting the NF-[Formula: see text]B pathway. In conclusion, QE is a new ferroptosis inducer and NF-[Formula: see text]B inhibitor that can not only induce ferroptosis, but also inhibit the invasion of ICC cells, providing a prospective strategy for the treatment of ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Ferroptose , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Linhagem Celular Tumoral , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genéticaRESUMO
With the rapid increase of diabetes cases in the world, there is an increasing demand for slowing down and managing diabetes and its effects. It is considered that a viable prophylactic treatment for type 2 diabetes mellitus (T2DM) is to reduce carbohydrate digestibility by controlling the activities of α-amylase and α-glucosidase to control postprandial hyperglycemia and promote the growth of intestinal beneficial bacteria. In this work, the effects of sulfonated lignin with different sulfonation degrees (0.8 mmol/g, SL1; 2.9 mmol/g, SL2) on the inhibition of α-amylase and α-glucosidase and the proliferation of intestinal beneficial bacteria in vitro were investigated. The results showed that both SL1 and SL2 can inhibit the activity of α-amylase and α-glucosidase. The inhibition capacity (IC50, 32.35 µg/mL) of SL2 with a low concentration (0-0.5 mg/mL) to α-amylase was close to that of acarbose to α-amylase (IC50, 27.33 µg/mL). Compared with the control groups, the bacterial cell concentrations of Bifidobacteria adolescentis and Lactobacillus acidophilus cultured with SL1 and SL2 increased in varying degrees (8-36%), and the produced short-chain fatty acids were about 1.2 times higher. This work demonstrates the prospect of sulfonated lignin as a prebiotic for the prevention and treatment of T2DM, which provides new insights for opening up a brand new field of lignin.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Lignina , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicemia , alfa-Glucosidases , alfa-Amilases , Extratos Vegetais/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tongguanteng injection (TGT), the water extract from the stem of the Traditional Chinese hebal medicine of Marsdenia tenacissima (Roxb.) Wight et Arn. has been used as anticancer remedy for decades. TGT was not only used in the treatment of many malignant cancers extensively, but also an adjuvant anticancer drug with chemotherapeutics clinically. AIM OF THE STUDY: To evaluate the effects of TGT on reversing paclitaxel (PTX) resistance and investigate the potential mechanism related to TAB1 in ovarian cancer (OC) in vitro and in vivo. MATERIALS AND METHODS: The synergistic effect and reversal ratio were determined by CCK8 assay and median-effect principle after the combination of TGT and PTX in OC A2780 and its PTX-resistant (A2780/T) cells. The biological functions in cell apoptosis, migration and invasion of A2780/T cells treated by PTX 4 µM with TGT 20, 40, 80 mgâ mL-1 for 24 h were evaluated by colony formation, flow cytometry, wound healing and transwell assays. Proteomics technique and bioinformatic analysis were used to indentify the change of TAB1 expression in A2780/T cells induced by TGT. The association between TAB1 expression and human OC was analyzed by gene expression databases. In A2780/T cells, western blotting and colony formation assays were used to investigate the relationship between TAB1 expression and PTX resistance after TAB1 overexpression by TAB1 plasmids. The mechanism of TGT and PTX regulating TAB1 and its related proteins were explored by western blotting and flow cytometry assays after TAB1 knock-down using siTAB1. Moreover, TUNEL staining, immunohistochemistry (IHC) and histopathology were used to observe the antitumor effects, TAB1 and p-p38 expression and the tissues impairments in nude mice xenograft model established by A2780/T cells after the co-treatment with TGT and PTX by in vivo. RESULTS: TGT combined with PTX showed the synergistic effect (CI<1), which could reverse the IC50 values of PTX in OC A2780 and A2780/T cells about 23.50 and 6.44 times, respectively. Besides, TGT combined with PTX could significantly inhibit the migration, invasion and promote apoptosis of A2780/T cells. We identified that TGT could induce TAB1 expression in A2780/T cells by proteomics analysis. TAB1 downregulation was significantly associated with tumorigenesis and poor prognosis in OC patients and PTX resistance in A2780/T cells. Furthermore, TGT could activate TAB1/TAK1/p38 MAPK signaling pathway targeting TAB1 and regulate the expression of Bax, Bcl-2 proteins to improve the sensitivity of A2780/T cells to PTX. TGT combined with PTX also showed a greater inhibition in tumor growth than PTX monotherapy in vivo. These promising results show the efficacy of TGT in reversing PTX resistance and provide a potential strategy that targeting TAB1/TAK1/p38 MAPK signaling pathway may improve the chemotherapy sensitivity in OC. CONCLUSIONS: Our results revealed that Tongguanteng injection could reverse paclitaxel resistance and the potential mechanism might be associated with the activation of TAB1/TAK1/p38 MAPK signaling pathway in OC in vitro and in vivo. TAB1 might be a pivotal target for reversing PTX resistance. This study will provide a theoretical basis for the combination of Tongguanteng injection and paclitaxel in clinic.
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Antineoplásicos Fitogênicos , Antineoplásicos , Neoplasias Ovarianas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Objective: To explore the clinical effects of fractional carbon dioxide laser combined with minimally invasive scar release in the treatment of post-acne atrophic scars. Methods: A retrospectively observational study was conducted. From January to June 2021, 60 patients with grade 3 and 4 post-acne atrophic scars who met the inclusion criteria were admitted to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. According to the adopted treatment methods, 30 patients treated with fractional carbon dioxide laser combined with minimally invasive scar release were included in combined treatment group (19 males and 11 females, aged (26±4) years), and 30 patients treated with fractional carbon dioxide laser alone were included in laser alone group (18 males and 12 females, aged (25±6) years). All the patients received the treatment once every two months, totally 3 times. Before the first treatment and 2 months after the last treatment, the scars were assessed by échelle d'évaluation clinique des cicatrices d'acné (ECCA). In 2 months after the last treatment, the curative effect was evaluated and the total effective rate was calculated according to the ECCA score. The adverse reactions of patients during the treatment were recorded. Data were statistically analyzed with independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: Before the first treatment, the ECCA scores of patients in the two groups were similar (P>0.05). In 2 months after the last treatment, the ECCA scores of patients in combined treatment group were significantly lower than those of laser alone group (Z=-2.89, P<0.05). The ECCA scores of patients in combined treatment group and laser alone group in 2 months after the last treatment were both significantly lower than those before the first treatment (with Z values of -4.81 and -4.79, respectively, P<0.05). In 2 months after the last treatment, the treatment in laser alone group cured the scars in 2 patients, and were markedly effective in 13 patients, effective in 7 patients, and ineffective in 8 patients; the treatment in combined treatment group cured the scars in 4 patients, and were markedly effective in 22 patients, effective in 3 patients, and ineffective in one patients. The total effective rate of scar treatment in combined treatment group (96.67%, 29/30) was significantly higher than 73.33% (22/30) in laser alone group (P<0.05). During treatment, in combined treatment group, 3 patients had pain, one patient had redness and swelling, and one patient had pigmentation. In laser alone group, one patient had pain, and 2 patients had pigmentation. No infection occurred in the wounds of all the patients in the two groups. Conclusions: Compared with fractional carbon dioxide laser alone, fractional carbon dioxide laser combined with minimally invasive scar release for post-acne atrophic scars can result in a higher total effective rate, with simple operation and good effect, so it is worthy of clinical application.
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Masculino , Feminino , Humanos , Cicatriz/terapia , Estudos Retrospectivos , Resultado do Tratamento , Lasers de Gás/uso terapêutico , Acne Vulgar , Atrofia , Dor , Dióxido de CarbonoRESUMO
BACKGROUND Previous studies have confirmed that progesterone has a protective effect on traumatic brain injury (TBI). In this paper, network pharmacology and molecular docking technology were used to further explore the potential mechanism of progesterone in the treatment of TBI. MATERIAL AND METHODS Based on network pharmacology, potential targets of progesterone for TBI were obtained. The network diagram of interactions between target proteins was established to screen the key targets of progesterone for TBI. The DAVID database was used to analyze its biological function and enrichment pathway, and to explore and determine the biological pathway of progesterone in treating TBI. Molecular docking technology was used to simulate the interaction between progesterone and key target proteins. RESULTS Progesterone can treat TBI by anti-inflammatory action, repairing damaged cell membranes, stabilizing the structure of the blood-brain barrier, alleviating brain edema, reducing neuronal apoptosis, and improving neurological function. The molecular mechanism involves the PI3K/Akt signaling pathway, MAPK signaling pathway, and Ras signaling pathway. CONCLUSIONS Progesterone is a potential clinical treatment for TBI. Exploring the potential targets and pathways of TBI therapy through network pharmacology can provide a direction for subsequent research.
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Lesões Encefálicas Traumáticas , Medicamentos de Ervas Chinesas , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Progesterona/farmacologia , Progesterona/uso terapêutico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , TecnologiaRESUMO
Background: Abdominal aortic aneurysm (AAA) is a degenerative disease that causes health problems in humans. However, there are no effective drugs for the treatment of AAA. Artemisia annua L. (A. annua) is a traditional herbal that has been widely used in cardiovascular disease. Based on network pharmacology and molecular docking technology, this study predicted the practical components and potential mechanisms of A. annua inhibiting the occurrence and development of AAA. Methods: The main active ingredients and targets of A. annua were screened through the TCMSP database; the GeneCards, OMIM, PharmGkb, and TTD databases were used to search for the targeted genes of AAA and map them to the targets of the active ingredients to obtain the active ingredient therapy of A. annua. The targets of AAA were to construct a protein interaction network through the STRING platform. R software was used to carry out the enrichment analysis of GO and KEGG for relevant targets, and Cytoscape was used to construct the active ingredient-target network prediction model of A. annua. Finally, AutoDock Vina was used to verify the results of the active ingredients and critical targets. Results: The main active ingredients obtained from A. annua for the treatment of AAA include quercetin, luteolin, kaempferol, isorhamnetin, and artemetin, as well as 117 effective targets, including RELA, MAPK14, CCND1, MAPK1, AKT1, MYC, MAPK8, TP53, ESR1, FOS, and JUN. The 11 targeted genes might play a key role in disease treatment. Enriched in 2115 GO biological processes, 159 molecular functions, 56 cellular components, and 156 KEGG pathways, inferred that its mechanism of action might be related to PI3K-Akt signaling pathway, fluid shear stress, atherosclerosis, and AGE-RAGE signaling pathway. Molecular docking results showed that the top five active components of A. annua had a good affinity for core disease targets and played a central role in treating AAA. The low binding energy molecular docking results provided valuable information for the development of drugs to treat AAA. Conclusion: Therefore, A. annua may have multiple components, multiple targets, and multiple signaling pathways to play a role in treating AAA. A. annua may have the potential to treat AAA.
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Triple-negative breast cancer (TNBC) is a form of breast cancer that is more aggressive and harder to treat than others, with a higher probability of relapse. Its nefarious capabilities for migrating and invading other parts of the body together with the current lack of clinically established effective therapies account for a low survival rate. In this work, we demonstrate the in-tandem use of two complementary therapeutic routes to effectively combat TNBC. A versatile magnetic-photothermal converter (MPC) consisting of zinc-doped ferrite nanoparticles and polyethene glycol, is shown to display excellent therapeutic efficiency, being capable to fight TNBC via two distinct routes: magneto-mechanical force (MMF) and near-infrared-II (NIR-II) hypothermal ablation. The combined use of these two complementary and synergistic therapies, which are less aggressive to the human body compared to conventional chemotherapeutic approaches, results in the splendid suppression of TNBC migration and invasion. Remotely controlling the MPCs by an external magnetic field, results in cellular MMF effects that cause direct mechanical destruction to the cancer cell membrane, leading to its necrosis. Furthermore, the MMF disrupts intracellular lysosomes, thereby triggering the release of large amounts of protein hydrolases, which induce intracellular oxidative stress, and accelerate the induction of apoptosis. Complementing the therapeutic approach based on MMF, the excellent photothermal performance of the MPC in the NIR-II region (1064 nm) is exploited to enable effective hypothermal ablation of the tumours, which can be achieved in deep tissue layers. The proposed multifunctional nanocomposites, together with the demonstrated "double-punch" therapeutic approach, hold significant potential to pave the way for future cutting-edge weapons against the dreadful TNBC.
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Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Fototerapia/métodos , Linhagem Celular Tumoral , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: The most effective treatment for knee joint pain is total knee arthroplasty (TKA), but the risk of pain and swelling in patients after surgery is high. Ice application, ankle pump exercise and non-steroidal anti-inflammatory painkillers are the primary clinical treatments after surgery. However, long-term use of non-steroidal anti-inflammatory pain relievers can easily cause gastrointestinal damage. Traditional Chinese medicine (TCM) ointments and tuina therapy integrate TCM and manipulation, which effectively promotes the penetration of TCM into the skin lesions, improves local blood circulation and inflammatory reaction and has good long-term effects on patients. AIM: To evaluate the efficacy of TCM ointment combined with tuina therapy in the treatment of pain and swelling after TKA. METHODS: The randomized controlled clinical trial enrolled 80 patients who underwent TKA via the same procedure. The patients were randomly divided among the treatment group (n = 40) and the control group (n = 40). The control group was given an analgesia pump in addition to oral painkillers as the postoperative intervention. The treatment group received TCM ointment with tuina therapy in addition to the analgesia pump and oral painkillers in the postoperative period. The following variables were recorded 3 d before surgery and 3 d, 7 d and 14 d after surgery: Visual analogue scale (VAS) score; skin temperature; circumferences at 15 cm above and below the patella; maximum active knee flexion angle; and the knee injury and Osteoarthritis Outcome score (KOOS). RESULTS: After treatment, VAS was significantly lower in the treatment group than the control group at 7 d (t = 7.536, P < 0.001) and 14 d (t = 8.563, P < 0.001). The skin temperature of participants in the treatment group was significantly lower than that in the control group at 7 d (t = 2.968, P = 0.004) and 14 d (t = 4.423, P < 0.001). The circumference values of the two positions in the treatment group were lower than those in the control group at 7 d [t = 2.315, P = 0.023 (above); t = 2.121, P = 0.037 (below)] and 14 d [t = 2.374, P = 0.020 (above); t = 2.095, P = 0.039 (below)]. After 14 d of treatment, the maximum active knee flexion angle and KOOS of the two groups were significantly improved but were significantly higher in the treatment group (P < 0.05 for both). CONCLUSION: TCM ointment and tuina therapy have significant advantages over standard care in the treatment of pain and swelling after TKA. This additional treatment may improve knee function but additional studies are needed to confirm our observations.
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Microplastics (<5 mm) are an emerging pollutant which have received increasing concern in recent years. Microplastics pose a serious hazard and potential risk to the environment due to their migration, transformation, adsorption and degradation properties. The effects of different types of microplastics on the elemental cycles (carbon, nitrogen and phosphorus cycles) in ecosystems were comprehensively summarized. The impacts of microplastics on the element cycle occur mainly in the soil environment and to less extent in other environments. Microplastics affect carbon sources, carbon dioxide (CO2) emissions, and carbon conversion processes, mainly by affecting plant and animal activities, changing gene abundance, enzyme activity, and microbial community composition. Microplastics can affect nitrogen sources, nitrogen fixation, ammonification, nitrification and denitrification processes by changing gene abundance, enzyme activity and microbial community composition. Microplastics can also influence phosphorus content and phosphorus conversion processes by stimulating enzyme activity and changing the composition of microbial communities. Future research needs to analyze the coupling of multiple microplastics and influencing factors on elemental cycling processes. This work provides a better view of the impacts of microplastics on element cycles and the interaction between microplastics and organisms.
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Poluentes Ambientais , Microbiota , Dióxido de Carbono/metabolismo , Ecossistema , Microplásticos , Nitrogênio/metabolismo , Fósforo , Plásticos/toxicidade , Solo , Microbiologia do SoloRESUMO
This study aims to explore the potential mechanism of Liangfu Pills in the treatment of functional dyspepsia(FD) based on network pharmacology and molecular docking, and verify the mechanism by animal experiment. The active components of Liangfu Pills were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of Liangfu Pills were predicted by SwissTargetPrediction. The targets of FD were retrieved from GeneCards. On this basis, the common targets of the disease and the pills were yielded and the protein interaction was retrieved based on STRING. The core targets were screened out, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis with DAVID. Finally, molecular docking was carried out with the help of AutoDock Tools to predict the binding degree between the effective components of Liangfu Pills and core targets. A total of 19 active components of Liangfu Pills and 591 FD-related targets were screened out by network pharmacology, of which 253 were common targets of the disease and the prescription. Liangfu Pills was mainly involved in the biological processes of response to drug, negative regulation of transcription, positive regulation of apoptotic process, and cell surface receptor signaling pathway, and the KEGG pathways of hypoxia-inducible factor-1(HIF-1) signaling pathway, serotonergic synapse, tumor necrosis factor(TNF) signaling pathway, cyclic adenosine monophosphate(cAMP) signaling pathway, calcium signal pathway, and inflammatory mediator regulation of transient receptor potential(TRP) channels. The results of molecular docking showed that the key active components of Liangfu Pills had certain binding activity to the targets mitogen-activated protein kinase 1(MAPK1), protein kinase B(AKT1), transient receptor potential cation channel subfamily V member 1(TRPV1), 5-hydroxytryptamine receptor 1 A(HTR1 A), and 5-hydroxytryptamine receptor 2 A(HTR2 A). FD was induced in rats, and then Liangfu Pills was given to FD rats for 7 days. The results showed that Liangfu Pills could significantly relieve the symptoms of FD rats, significantly increase the expression of 5-hydroxytryptamine(5-HT), and down-regulate the expression of TRPV1. Through network pharmacology, molecular docking, and experimental verification, this study proved that Liangfu Pills improved FD through multiple components and multiple targets. The result lays a basis for further research on the mechanism and clinical application of Liangfu Pills in the treatment of FD.
Assuntos
Medicamentos de Ervas Chinesas , Dispepsia , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , RatosRESUMO
Background: To explore the effect of combining traditional Chinese medicine (TCM) and Western medicine in hemodialysis patients with coronavirus disease 2019 (COVID-19). Methods: This study was conducted from 27 January 2020 to 17 March 2020 in Wuhan Third Hospital Guanggu Branch, Wuhan, China. Fifty-three patients were included and divided into a control group (CG), which received Western medicine and a combined treatment group, which received TCM and Western medicine (TG). Clinical and laboratory data, TCM symptom scores, and chest computed tomography results were extracted and compared between the two groups. Results: The TG included 21 (67.7%) men and 10 (32.3%) women with a mean age of 61.02 (standard deviation [SD] 15.07, range 26-89) years. The mean dialysis duration in the TG was 49 (SD 31) months. Of all patients in the TG, 27 (87.1%) had fatigue, 18 (58.1%) had dry cough, 16 (51.6%) had anorexia, 11 (35.5%) had dyspnea, and 11 (35.5%) had fever. The CG included 14 (63.6%) men and 8 (36.4%) women with a mean age of 61.45 (SD 13.78, range 36-84) years. The mean dialysis duration in the CG was 63 (SD 46) months. Of all patients in the CG, 21 (95.5%) had fatigue, 12 (54.5%) had dry cough, 17 (77.3%) had anorexia, 12 (54.5%) had dyspnea, and 7 (31.8%) had fever. After treatment, the TCM symptom scores of the two groups decreased; the anorexia scores were lower in the TG than in the CG (p < 0.05). After treatment, albumin increased and D-dimer, C-reactive protein, and lactate dehydrogenase levels decreased in the TG. The d-dimer levels were lower and the albumin level was higher in the TG than in the CG after treatment (p < 0.05). The cure rate was higher, and the mortality rate was lower in the TG than in the CG (p < 0.05). Conclusion: A combination of TCM and Western medicine in hemodialysis patients with COVID-19 could relieve symptoms and help recovery. Further evidence from larger randomized controlled trials is needed to confirm our results.
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Objective: The current review was aimed to determine the effectiveness of mental imagery training (MIT) on the enhancement of maximum voluntary muscle contraction (MVC) force for healthy young and old adults. Data sources: Six electronic databases were searched from July 2021 to March 2022. Search terms included: "motor imagery training," "motor imagery practice," "mental practice," "mental training," "movement imagery," "cognitive training," "strength," "force," "muscle strength," "performance," "enhancement," "improvement," "development," and "healthy adults." Study selection and data extraction: Randomized controlled trials of MIT in enhancing muscle strength with healthy adults were selected. The decision on whether a study met the inclusion criteria of the review was made by two reviewers independently. Any disagreements between the two reviewers were first resolved by discussion between the two reviewers. If consensus could not be reached, then it would be arbitrated by a third reviewer. Data synthesis: Twenty-five studies including both internal MIT and external MIT were included in meta-analysis for determining the efficacy of MIT on enhancing muscle strength and 22 internal MIT were used for subgroup analysis for examining dose-response relationship of MIT on MVC. Results: MIT demonstrated significant benefit on enhancing muscle strength when compared with no exercise, Effect Size (ES), 1.10, 95% confidence interval (CI), 0.89-1.30, favoring MIT, but was inferior to physical training (PT), ES, 0.38, 95% CI, 0.15-0.62, favoring PT. Subgroup analysis demonstrated that MIT was more effective for older adults (ES, 2.17, 95% CI, 1.57-2.76) than young adults (ES, 0.95, 95% CI, 0.74-1.17), p = 0.0002, and for small finger muscles (ES, 1.64, 95% CI, 1.06-2.22) than large upper extremity muscles (ES, 0.86, 95% CI, 0.56-1.16), p = 0.02. No significant difference was found in the comparison of small finger muscles and large lower extremity muscles, p = 0.19 although the ES of the former (ES, 1.64, 95% CI, 1.06-2.22) was greater than that of the later (ES, 1.20, 95%, 0.88-1.52). Conclusion: This review demonstrates that MIT has better estimated effects on enhancing MVC force compared to no exercise, but is inferior to PT. The combination of MIT and PT is equivalent to PT alone in enhancing muscle strength. The subgroup group analysis further suggests that older adults and small finger muscles may benefit more from MIT than young adults and larger muscles.
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The cuticular wax layer in fruit is a hydrophobic barrier which protects fruit from biotic and abiotic stress. The cuticular wax also affect fruit quality. This paper investigated the effects of salicylic acid on fruit quality and the cuticular wax in blueberry fruit during storage at room temperature (25 °C). 'Powderblue' blueberries (Vaccinium virgatum Ait) were treated with 1.0 mmol L-1 salicylic acid. The composition of cuticular wax layer and structure of epicuticular wax layer were analyzed at 4 d intervals during storage. Salicylic acid could efficiently delay the reduction of total wax content and affected the proportions of its constituents, including triterpenoids, esters, sterols, fatty acids, alcohols and alkanes. Our results also showed that there was no significant difference on the structure of epicuticular wax in salicylic acid treated fruits compared with that of the control. Salicylic acid delayed deterioration of blueberry fruit and enhanced its resistance to disease during storage.