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Traditional uses, phytochemistry, pharmacology, toxicity and clinical application of traditional Chinese medicine Cynoglossum amabile: a review.
Fan, Y, Wang, M, Zhang, Q, Ouyang, S, Mao, W, Xu, C, Wang, M, Long, C
Frontiers in pharmacology. 2024;:1325283
Abstract
Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.
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DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas.
Bildik, G, Gray, JP, Mao, W, Yang, H, Ozyurt, R, Orellana, VR, De Wever, O, Carey, MS, Bast, RC, Lu, Z
Autophagy. 2024;(3):675-691
Abstract
Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal CDKN1B/p27 localization, and inducing autophagic gene expression. Treatment with chloroquine or the novel dimeric chloroquine analog DC661 significantly enhances DIRAS3-mediated inhibition of mutant KRAS tumor cell growth in vitro and in vivo. Taken together, our study demonstrates that DIRAS3 plays a critical role in regulating mutant KRAS-driven oncogenesis in PDAC and LGSOC.Abbreviations: AFR: autophagic flux reporter; ATG: autophagy related; CQ: chloroquine; DCFDA 2'-7'-dichlorodihydrofluorescein diacetate; DIRAS3: DIRAS family GTPase 3; DOX: doxycycline; KRAS KRAS proto-oncogene, LGSOC low-grade serous ovarian cancer; MiT/TFE: microphthalmia family of transcription factors; NAC: N-acetylcysteine; PDAC pancreatic ductal adenocarcinoma; ROS: reactive oxygen species; TFEB transcription factor EB.
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Nutrition therapy in critically ill patients with severe acute pancreatitis.
Sun, JK, Lv, C, Gao, L, Mao, W, Li, W, Ke, L
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2024;(2):271-280
Abstract
A significant proportion of patients (10%-20%) with acute pancreatitis develop severe acute pancreatitis characterized by pancreatic necrosis, systemic inflammation, and organ failure, commonly requiring intensive care unit (ICU) admission. In this specific population, nutrition therapy is more challenging than that in the general ICU population, primarily because of inevitable gastrointestinal involvement by pancreatic inflammation. In this review, we discussed several key aspects of nutrition therapy in this population, including key pathophysiology that may impede nutrition therapy, the timing and implementation of enteral nutrition and parenteral nutrition, the importance of specific nutrient supplements, and the long-term outcomes that may be addressed by nutrition therapy.
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Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.
Zhang, Y, Qu, Z, Lu, T, Shao, X, Cai, M, Dilimulati, D, Gao, X, Mao, W, Hu, F, Su, L, et al
Nutrients. 2023;15(3)
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Polycystic ovary syndrome (PCOS) is a unification of reproductive endocrine and metabolic disorders. Lifestyle and weight management, particularly dietary intake aimed at weight loss, are initial treatment strategies for PCOS. A calorie-restricted diet (CRD) seems to be the optimal dietary pattern for weight management in the PCOS population. The aim of this study was to evaluate modifications in fat distribution, the androgenic state, and metabolic profiles in the overweight and obese PCOS-affected population, who obtained modest and equivalent weight loss induced by a CRD regimen with or without Dulaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA). This study was a randomised controlled trial which enrolled 68 females diagnosed with PCOS. Participants were randomly assigned to receive to one of the two groups: a GLP-1 RA combined with CRD or CRD alone. Results showed that participants in the GLP-1 RA + CRD group took a shorter time to achieve a 7% weight loss goal than those in the CRD group. Furthermore, both interventions had similar positive effects in improving menstrual frequency and reducing levels of blood pressure, insulin, aminotransferases, lipids, total fat mass, total lean mass, and abdominal subcutaneous adipose tissue mass after equivalent weight loss. Authors conclude that their findings support the importance of dietary intervention as a first-line treatment in women with PCOS, and that GLP-1 RA therapy offers an effective and generally tolerable adjunct therapy to aid in achieving weight targets based on dietary therapy in overweight and obese women with PCOS.
Abstract
The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.
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Reactive X (where X = O, N, S, C, Cl, Br, and I) species nanomedicine.
Wang, K, Mao, W, Song, X, Chen, M, Feng, W, Peng, B, Chen, Y
Chemical Society reviews. 2023;(20):6957-7035
Abstract
Reactive oxygen, nitrogen, sulfur, carbonyl, chlorine, bromine, and iodine species (RXS, where X = O, N, S, C, Cl, Br, and I) have important roles in various normal physiological processes and act as essential regulators of cell metabolism; their inherent biological activities govern cell signaling, immune balance, and tissue homeostasis. However, an imbalance between RXS production and consumption will induce the occurrence and development of various diseases. Due to the considerable progress of nanomedicine, a variety of nanosystems that can regulate RXS has been rationally designed and engineered for restoring RXS balance to halt the pathological processes of different diseases. The invention of radical-regulating nanomaterials creates the possibility of intriguing projects for disease treatment and promotes advances in nanomedicine. In this comprehensive review, we summarize, discuss, and highlight very-recent advances in RXS-based nanomedicine for versatile disease treatments. This review particularly focuses on the types and pathological effects of these reactive species and explores the biological effects of RXS-based nanomaterials, accompanied by a discussion and the outlook of the challenges faced and future clinical translations of RXS nanomedicines.
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Hydrocortisone Combined with Vitamin C and Thiamine in the Treatment of Sepsis/Septic Shock: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.
Lu, D, Mao, W
Clinical and investigative medicine. Medecine clinique et experimentale. 2023;(1):E36-49
Abstract
BACKGROUND This study explored the efficacy of hydrocortisone combined with vitamin C and thiamine (HVT) in the treatment of sepsis/septic shock. METHODS PubMed, EMBASE and Web of Science were searched (establishment of the database to October 31, 2022). The meta-analysis included randomized controlled trials (RCTs); comparing the efficacy of HVT regimen and placebo in the treatment of sepsis/septic shock. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias. The Review Manager 5.4 software was used for meta-analysis, and the relative risk (RR), mean difference (MD) and 95% confidence intervals (CI) were then determined. Trial sequential analysis (TSA) was then conducted. RESULTS Eight RCTs with 1,572 patients were identified. Meta-analysis showed that HVT regimen did not reduce all-cause (RR=0.96, 95% CI: 0.83 - 1.11, P=0.60), hospital (RR=1.03, 95% CI: 0.83 - 1.27, P=0.80) or intensive care unit (ICU) mortalities (RR=1.05, 95% CI: 0.86 - 1.28, P=0.65). Furthermore, there was no significant difference in the change of sequential organ failure assessment score, length of ICU stay, length of hospital stay, duration of the use of vasopressors, incidence of acute kidney injury and ventilator-free days between HVT and control groups. TSA showed that more trials are needed to confirm the results. CONCLUSIONS HVT regimen did not reduce the mortality of patients with sepsis/septic shock and was not associated with a significant improvement in outcomes. The TSA result showed that more RCTs with high quality and large sample sizes are needed to further confirm the results.
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Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions.
Yu, CC, Li, Y, Cheng, ZJ, Wang, X, Mao, W, Zhang, YW
Frontiers in pharmacology. 2022;:818179
Abstract
Multiple myeloma (MM) is a hematological malignancy characterized by clonal expansion of plasma cells in bone marrow, leading to the overproduction of monoclonal immunoglobulins. The clinical manifestations resulting from monoclonal proteins and malignant cells include signs of end-organ damage, such as hypercalcemia, renal failure, anemia, and bone lesions. Despite improvement in the survival of MM patients with use of myeloma-targeted and immunomodulatory therapies, MM remains an incurable disease. Moreover, patients with relapsed or refractory MM show poor survival outcomes. In recent years, there has been a growing interest in the use of traditional Chinese medicinal materials (TCMMs) for management of a wide spectrum of diseases. The bioactive ingredients derived from TCMMs hold great potential for the development of anticancer drugs. Here we summarize the evidence of the pharmacological effects of the active components in TCMMs on MM, including curcumin, resveratrol, baicalein, berberine, bufalin, cinobufagin, gambogic acid, ginsenoside, icariin, daidzin, formononetin, polysaccharides extracts from Hedyotis difus, and scutellarein. Available evidence indicates that the anti-MM effects of these bioactive ingredients are mediated via regulation of proliferation, apoptosis, autophagy, cell cycle, osteogenic differentiation, and drug resistance. In the future, the underlying mechanisms of the anti-MM effects of these components should be further investigated. Large-scale and well-designed clinical trials are also required to validate the efficacy of these bioactive constituents for MM.
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Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.
, , Wulf Hanson, S, Abbafati, C, Aerts, JG, Al-Aly, Z, Ashbaugh, C, Ballouz, T, Blyuss, O, Bobkova, P, Bonsel, G, et al
JAMA. 2022;(16):1604-1615
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Abstract
IMPORTANCE Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). OBJECTIVE To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. DESIGN, SETTING, AND PARTICIPANTS Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. EXPOSURES Symptomatic SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. RESULTS A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. CONCLUSIONS AND RELEVANCE This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
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Induced radiation studies and personnel dose assessment in a carbon ion therapy facility.
Luo, C, Li, W, Yang, B, Su, Y, Li, Y, Li, Z, Mao, W, Liu, X, Yan, W, Ma, F
Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. 2022;:110350
Abstract
Carbon ions have become the most widely used particles in heavy-ion tumor therapy due to favorable physical and biological characteristics. The beam delivery system (BDS) and tumor tissues are directly bombarded with accelerated carbon ions, resulting in activation products in the components and the patient's body. The results of an experimental study and a Monte-Carlo simulation for the radioactivity induced in a treatment room under a uniform scanning mode were presented in this study. They indicated that the multi-leaf collimator (MLC) and the patient's body were the main sources of induced radioactivity. The half-lives of the main produced radionuclides ranged from a few minutes to tens of minutes for single irradiation and from dozens of days to hundreds of days for long-term irradiation. The personal dose of medical staff working in the treatment room and the additional dose of the patient from the induced radioactivity were estimated. Finally, some suggestions were made to reduce the unwanted radiation exposure of the medical staff, patients, and carers.
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Natural medicines of targeted rheumatoid arthritis and its action mechanism.
Liu, X, Wang, Z, Qian, H, Tao, W, Zhang, Y, Hu, C, Mao, W, Guo, Q
Frontiers in immunology. 2022;:945129
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease involving joints, with clinical manifestations of joint inflammation, bone damage and cartilage destruction, joint dysfunction and deformity, and extra-articular organ damage. As an important source of new drug molecules, natural medicines have many advantages, such as a wide range of biological effects and small toxic and side effects. They have become a hot spot for the vast number of researchers to study various diseases and develop therapeutic drugs. In recent years, the research of natural medicines in the treatment of RA has made remarkable achievements. These natural medicines mainly include flavonoids, polyphenols, alkaloids, glycosides and terpenes. Among them, resveratrol, icariin, epigallocatechin-3-gallate, ginsenoside, sinomenine, paeoniflorin, triptolide and paeoniflorin are star natural medicines for the treatment of RA. Its mechanism of treating RA mainly involves these aspects: anti-inflammation, anti-oxidation, immune regulation, pro-apoptosis, inhibition of angiogenesis, inhibition of osteoclastogenesis, inhibition of fibroblast-like synovial cell proliferation, migration and invasion. This review summarizes natural medicines with potential therapeutic effects on RA and briefly discusses their mechanisms of action against RA.