Efficacy and Safety of Huashi Baidu Granules in the Treatment of Children Suffering from Influenza with Exterior-cold and Interior-heat Syndrome: A Multi-center, Randomized Controlled Trial Protocol.

Background: Influenza is one of the major public health problems worldwide. Children are the high-risk group for influenza and the high-risk population with symptoms. Huashi Baidu(HSBD) Granules have played a great role in fighting against COVID-19. In recent decades, this recipe has also been applied by pediatricians to treat influenza, with remarkable curative effects. However, there is still a lack of high-quality evidence-based medical practice. Methods: This study was designed as a multi-center, randomized, parallel-controlled trial, with an estimated sample size of 520 children suffering from influenza with exterior-cold and interior-heat syndrome. All the enrolled children will be randomly assigned to a test group and a control group. Children in the test group were treated with Huashi Baidu Granules, and those in the control group were provided with Oseltamivir Phosphate Granules for intervention. The primary outcome measure was the time to clinical recovery, with the Chinese version of the Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score measured at baseline and every 24 hours after treatment, which was evaluated at the endpoint of follow-up. The secondary outcome was the time to complete fever remission, scores of CARIFS symptom dimensions and the area under the curve with time, the incidence of complications/severe/critical influenza, the rate of single symptom disappearance, and the therapeutic effect of traditional Chinese medicine syndromes, which were recorded at baseline and after treatment, and evaluated at the end of treatment. Safety and endpoint events were evaluated at the same time. Conclusion: This study is intended to apply Huashi Baidu Granules to treat influenza with exterior-cold and interior-heat syndrome to identify the clinical efficacy and safety of this recipe. Simultaneously, our study will also discuss the characteristics of clinical syndrome in traditional Chinese medicine and syndrome distribution of influenza in the studied children.

Phytohormone Response of Drought-Acclimated Illicium difengpi (Schisandraceae).

Illicium difengpi (Schisandraceae), which is an endemic, medicinal, and endangered species found in small and isolated populations that inhabit karst mountain areas, has evolved strategies to adapt to arid environments and is thus an excellent material for exploring the mechanisms of tolerance to severe drought. In experiment I, I. difengpi plants were subjected to three soil watering treatments (CK, well-watered treatment at 50% of the dry soil weight for 18 days; DS, drought stress treatment at 10% of the dry soil weight for 18 days; DS-R, drought-rehydration treatment at 10% of the dry soil weight for 15 days followed by rewatering to 50% of the dry soil weight for another 3 days). The effects of the drought and rehydration treatments on leaf succulence, phytohormones, and phytohormonal signal transduction in I. difengpi plants were investigated. In experiment II, exogenous abscisic acid (ABA, 60 mg L-1) and zeatin riboside (ZR, 60 mg L-1) were sprayed onto DS-treated plants to verify the roles of exogenous phytohormones in alleviating drought injury. Leaf succulence showed marked changes in response to the DS and DS-R treatments. The relative concentrations of ABA, methyl jasmonate (MeJA), salicylic acid glucoside (SAG), and cis-zeatin riboside (cZR) were highly correlated with relative leaf succulence. The leaf succulence of drought-treated I. difengpi plants recovered to that observed with the CK treatment after exogenous application of ABA or ZR. Differentially expressed genes involved in biosynthesis and signal transduction of phytohormones (ABA and JA) in response to drought stress were identified by transcriptomic profiling. The current study suggested that the phytohormones ABA, JA, and ZR may play important roles in the response to severe drought and provides a preliminary understanding of the physiological mechanisms involved in phytohormonal regulation in I. difengpi, an endemic, medicinal, and highly drought-tolerant plant found in extremely small populations in the karst region of South China.

Risk factors for severe and critically ill COVID-19 patients: A review.

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused an unprecedented global social and economic impact, and high numbers of deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, Krebs von den Lungen-6 (KL-6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID-19.

LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p.

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.

LncRNA MIAT facilitates osteosarcoma progression by regulating mir-128-3p/VEGFC axis.

The aberrant expression of long non-coding RNAs (lncRNAs) has been involved in the progression of many human tumors including osteosarcoma (OS). However, the biological function and the underlying mechanism of the lncRNA myocardial infarction-associated transcript (MIAT) in OS remain unclear. In the present study, we found that lncRNA MIAT was significantly up-regulated in both OS tissues and cell lines, and high expression of MIAT was positively associated with tumor size and lymph node metastasis of OS patients. In addition, knockdown of MIAT inhibited proliferation, migration, invasion and promoted apoptosis of OS cells in vitro. Moreover, the expression of MIAT was negatively associated with miR-128-3p but positively correlated with vascular endothelial growth factor C (VEGFC) in OS. Further mechanistic study revealed that lncRNA MIAT promoted OS progression by up-regulating VEGFC via sponging miR-128-3p in vitro. Taken together, our results suggest that MIAT/miR-128-3p/VEGFC axis contributes to OS progression and may be used as a novel therapeutic target for OS. © 2019 IUBMB Life, 9999(9999):1-9, 2019.

Metabolic effects of breastfeed in women with prior gestational diabetes mellitus: A systematic review and meta-analysis.

This study was undertaken to provide comprehensive analyses of current research developments in the field of breastfeed (BF) and metabolic-related outcomes among women with prior gestational diabetes mellitus (GDM). Database PubMed, Embase, BIOSIS Previews, Web of Science, and Cochrane Library were searched through December 3, 2017. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were pooled by random-effects model using Stata version 12.0. Twenty-three observational studies were included in quantitative synthesis. Reduced possibility of progression to type 2 diabetes mellitus (T2DM; OR = 0.79; 95% CI, 0.68-0.92) and pre-DM (OR = 0.66; 95% CI, 0.51-0.86) were found among women with longer BF of any intensity after GDM pregnancy. The positive effect of longer BF on progression to T2DM gradually became prominent with the extension of follow-up period. Compared with women with shorter BF, those with longer BF manifested more favourable metabolic parameters, including significant lower body mass index, fasting glucose, triglyceride, and higher insulin sensitivity index. The findings support that BF may play an important role in protection against the development of T2DM-related outcomes in midlife of women with prior GDM. However, further studies are needed to reveal the etiological mechanism.

Insulin promotes progression of colon cancer by upregulation of ACAT1.

BACKGROUND: Insulin resistant and the progression of cancer is closely related. The aim of this study was to  investigate the effect of insulin on the proliferation and migration of colon cancer cells and its underlying mechanism. METHODS: Colon carcinoma tissues from the 80 cases of colon cancer patients were collected. Immunohistochemistry was used to detect the expression of acyl coenzyme A: cholesterol acyltransferase1 (ACAT1), and we analyzed the correlation between hyperglycemia and ACAT1, hyperglycemia and metastasis. CCK8 assay and transwell assay were used to investigate the effect of different concentrations of insulin and ACAT1siRNA on human colon cancer cell line HT-29. ACAT1 mRNA expression and protein level in HT-29 cells were determined by real-time quantitative PCR and western blotting, respectively. RESULTS: Biopsies from patients with colon carcinoma showed hyperglycemia links ACAT1, lymph nodes metastasis and distant metastasis. Insulin markedly promoted cell proliferation and migration in human colon cancer HT-29 cells. Moreover, ACAT1mRNA expression and protein level were increased by insulin. ACAT1siRNA resulted in a complete inhibition of the ACAT1 mRNA expression. Consequently insulin-triggered cell proliferation and migration on colon cancer cells were inhibited. CONCLUSION: The progression of colon cancer has a positive correlation with hyperinsulinemia. Insulin-triggered cell proliferation and metastatic effects on colorectal cancer cells are mediated by ACAT1. Therefore, insulin could promote colon cancer progression by upregulation of ACAT1, which maybe is a potential therapeutic target for colon cancer.

Risk factors of renal dysfunction and their interaction in level-low lead exposure paint workers.

BACKGROUND: To explore the effect of low-level lead exposure on renal dysfunction in paint works, and analyze the interaction between low-level lead exposure and other influence factors of renal dysfunction. METHODS: Seven hundred forty seven workers from Sany Heavy Industry Company and Xiangjiang Kansai Paint Company who have been exposed to paint were chosen by random cluster sampling. Their blood lead level and Urine ß2-micro globulin level (renal dysfunction) were tested,risk factors of renal dysfunction in paint workers and their interactions were analyzed. RESULTS: The prevalence of renal dysfunction was 12.37%. Risk factors of renal dysfunction in paint workers mainly included longer working years (OR = 1.699, 95% CI: 1.226~ 2.355), blood lead positive (OR = 2.847, 95% CI: 1.577~ 5.139) and hypertension (OR = 2.192, 95% CI: 1.103~ 4.359). Positive interaction existed between hypertension and low-level blood lead on renal dysfunction in paint workers, the RERI (Relative excess risk of interaction), API (Attributable proportions of interaction) and S(the synergy index) were 4.758, 54.5% and 2.604 respectively. CONCLUSIONS: Low-level lead exposure and hypertension not only have independent effect on renal dysfunction in paint workers, but also had obvious positive interaction in paint workers. Interventions aimed at blood lead and blood pressure at the same time will better prenvent from renal dysfunction.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

Clinical Implications of Estimating Glomerular Filtration Rate with Different Equations in Heart Failure Patients with Preserved Ejection Fraction.

INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and  < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or  < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.

Loss of flrt2 gene leads to microphthalmia in zebrafish.

As a member of the fibronectin leucine-rich transmembrane (flrt) gene family, fibronectin leucine-rich transmembrane 2 (flrt2) is strongly expressed in a subset of sclerotome cells, and the resultant protein interacts with FGFR1 in the FGF signaling pathway during development. Studies on flrt2 have focused mainly on its roles in the brain, heart and chondrogenesis. However, reports on its expression and function in the zebrafish retina are lacking. Here, we detected the high expression of flrt2 in zebrafish retina using in situ hybridization technique and developed an flrt2-knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. Quantitative real-time PCR was used to measure the expression levels of flrt2, which results in an approximately 60% mRNA reduction. The flrt2-KO zebrafish eyes' altered morphological, cellular, and molecular events were identified using BrdU labeling, TUNEL assay, immunofluorescent staining, fluorescent dye injection and RNA sequencing. Abnormal eye development, known as microphthalmia, was found in flrt2-KO larvae, and the retinal progenitor cells exhibited increased apoptosis, perhaps owing to the combined effects of crx, neurod4, atoh7, and pcdh8 downregulation and Casp3a and Caspbl upregulation. In contrast, the retinal neural development, as well as retinal progenitor cell differentiation and proliferation, were not affected by the flrt2 deletion. Thus, flrt2 appears to play important roles in retinal development and function, which may provide the basis for further investigations into the molecular mechanisms of retinal development and evolution.

Transcriptomic and metabolomic profiling reveals the drought tolerance mechanism of Illicium difengpi (Schisandraceae).

Illicium difengpi (Schisandraceae), an endangered medicinal plant endemic to karst areas, is highly tolerant to drought and thus can be used as an ideal material for investigating adaptive mechanism to drought stress. The understanding of the drought tolerance of I. difengpi, especially at the molecular level, is lacking. In the present study, we aimed to clarify the molecular mechanism underlying drought tolerance in endemic I. difengpi plant in karst regions. The response characteristics of transcripts and changes in metabolite abundance of I. difengpi subjected to drought and rehydration were analyzed, the genes and key metabolites responsive to drought and rehydration were screened, and some important biosynthetic and secondary metabolic pathways were identified. A total of 231,784 genes and 632 metabolites were obtained from transcriptome and metabolome analyses, and most of the physiological metabolism in drought-treated I. difengpi plants recovered after rehydration. There were more upregulated genes than downregulated genes under drought and rehydration treatments, and rehydration treatment induced stable expression of 65.25% of genes, indicating that rehydration alleviated drought stress to some extent. Drought and rehydration treatment generated flavonoids, phenolic acids, flavonols, amino acids and their derivatives, as well as metabolites such as saccharides and alcohols in the leaves of I. difengpi plants, which alleviated the injury caused by excessive reactive oxygen species. The integration of transcriptome and metabolome analyses showed that, under drought stress, I. difengpi increased glutathione, flavonoids, polyamines, soluble sugars and amino acids, contributing to cell osmotic potential and antioxidant activity. The results show that the high drought tolerance and recovery after rehydration are the reasons for the normal growth of I. difengpi in karst mountain areas.

Establishment of an efficient transformation system and its application in regulatory mechanism analysis of biological macromolecules in tea plants.

Tea (Camellia sinensis), one of the most important beverage crops originated from China and is now cultivated worldwide, provides numerous secondary metabolites that account for its health benefits and rich flavor. However, the lack of an efficient and reliable genetic transformation system has seriously hindered the gene function investigation and precise breeding of C. sinensis. In this study, we established a highly efficient, labor-saving, and cost-effective Agrobacterium rhizogenes-mediated hairy roots genetic transformation system for C. sinensis, which can be used for gene overexpression and genome editing. The established transformation system was simple to operate, bypassing tissue culture and antibiotic screening, and only took two months to complete. We used this system to conduct function analysis of transcription factor CsMYB73 and found that CsMYB73 negatively regulates L-theanine synthesis in tea plant. Additionally, callus formation was successfully induced using transgenic roots, and the transgenic callus exhibited normal chlorophyll production, enabling the study of the corresponding biological functions. Furthermore, this genetic transformation system was effective for multiple C. sinensis varieties and other woody plant species. By overcoming technical obstacles such as low efficiency, long experimental periods, and high costs, this genetic transformation will be a valuable tool for routine gene investigation and precise breeding in tea plants.

Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue.

Wnt5a is a member of the Wnt family of secreted glycoproteins that play essential organizing roles in development. Similar to other Wnt members, Wnt5a can upregulate cell proliferation and has been proposed to have oncogenic function. Here we report that Wnt5a signals through the noncanonical Wnt/Ca++ pathway to suppress cyclin D1 expression and negatively regulate B cell proliferation in a cell-autonomous manner. Wnt5a hemizygous mice develop myeloid leukemias and B cell lymphomas that are clonal in origin and display loss of Wnt5a function in tumor tissues. Furthermore, analysis of human primary leukemias reveals deletion of the WNT5A gene and/or loss of WNT5A expression in a majority of the patient samples. These results demonstrate that Wnt5a suppresses hematopoietic malignancies.

Biophysical characteristics of meridians and acupoints: a systematic review.

As an integral part of traditional Chinese medicine (TCM), acupuncture is a convenient and effective therapy with fewer adverse effects. Recently, researches on meridian essence have become core issues of modern TCM. Numerous experiments have demonstrated the objective existence of meridians by different technologies since 1950s, such as biophysics, biochemistry, and molecular biology. In this paper, we review biophysical studies on electric, acoustic, thermal, optical, magnetic, isotopic, and myoelectric aspects of meridians and acupoints. These studies suggest that meridians/acupoints have biophysical characteristics which are different from nonacupuncture points. Owing to the limitations of previous studies, future research using high-throughput technologies such as omics and multicenter randomized controlled trials should be performed to explore the acupuncture's mechanisms of action and demonstration of efficacy.

Effects of light intensity on the growth of Polygala fallax Hemsl. (Polygalaceae).

Polygala fallax Hemsl. (Polygalaceae), a traditional Chinese medicinal species, requires optimal growth conditions for artificial cultivation. Irradiance is one of the primary environmental factors that affects the growth and survival of P. fallax Hemsl. plants, which seemingly grow better under weak irradiance conditions. However, the optimum light intensity for growing P. fallax Hemsl. is not clear. To determine the optimum light intensity for cultivating this medicinal plant species, P. fallax Hemsl. plants from two different habitats were grown and exposed to three shade treatments (50% shade, 70% shade and 90% shade, which resulted in photosynthetically active radiation amounts equal to 662 µmol m-2 s-1, 401 µmol m-2 s-1, and 131 µmol m-2 s-1, respectively) to evaluate survival, growth, leaf photosynthesis, and the main pharmacological active ingredients (saponins) in response to shade. Our results revealed that the P. fallax Hemsl. plants in the different habitats consistently exhibited relatively high photosynthesis rates, biomass, survival rates and saponins under 662 µmol m-2 s-1 created by the 50% shade treatment. We concluded that photosynthetically active radiation of approximately 662 µmol m-2 s-1 is suitable for the cultivation of P. fallax Hemsl. plants.

An Integrated Metabolome and Transcriptome Analysis Reveal the Regulation Mechanisms of Flavonoid Biosynthesis in a Purple Tea Plant Cultivar.

Purple tea plant cultivars, enrich with flavonoids and anthocyanins, are valuable materials for manufacturing tea with unique color and flavor. Researchers found that 'Zijuan' leaves changed from purple to green mainly caused by the decreased flavonoids and anthocyanins concentrations. The mechanism of flavonoids and anthocyanin biosynthesis has been studied in many purple tea plant cultivars and the key genes which regulated the biosynthesis of flavonoid and anthocyanins in different purple tea plant cultivars were quite different. Also, the molecular regulation mechanism underlying the flavonoids and anthocyanins biosynthesis during leaves development and color changes is less-thoroughly understood. In this study, an integrative analysis of transcriptome and metabolome was performed on the purple leaves and green leaves of 'Zijuan' tea plant to reveal the regulatory networks correlated to flavonoid biosynthesis and to identify key regulatory genes. Our results indicated that the 'Zijuan' new shoots leaves were purple might be due to the copigmentation of quercetin and kaempferol derivatives. In 'Zijuan' tea plant cultivar, flavonoids metabolites concentrations in purple leaves and green leaves were significantly influenced by the genes involved in flavonoid biosynthesis, transcriptional regulation, transport, and hormone response. Transcription factors including NAC008, MYB23, and bHLH96 and transporters such as ABC transporter I might be responsible for the flavonoid and anthocyanins accumulation in purple leaves. This study provides a new insight into the metabolism and molecular mechanisms underlying flavonoid and anthocyanin biosynthesis in tea plant.

Combining Network Pharmacology and Experimental Validation to Study the Action and Mechanism of Water extract of Asparagus Against Colorectal Cancer.

Asparagus (ASP) is a well-known traditional Chinese medicine with nourishing, moistening, fire-clearing, cough-suppressing, and intestinal effects. In addition, it exerts anti-inflammatory, antioxidant, anti-aging, immunity-enhancing, and anti-tumor pharmacological effect. The anti-tumor effect of ASP has been studied in hepatocellular carcinoma. However, its action and pharmacological mechanism in colorectal cancer (CRC) are unclear. The present study aimed to identify the potential targets of ASP for CRC treatment using network pharmacology and explore its possible therapeutic mechanisms using in vitro and in vivo experiments. The active compounds and potential targets of ASP were obtained from the TCMSP database, followed by CRC-related target genes identification using GeneCards and OMIM databases, which were matched with the potential targets of ASP. Based on the matching results, potential targets and signaling pathways were identified by protein-protein interaction (PPI), gene ontology (GO) functions, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, in vitro and in vivo experiments were performed to further validate the anti-cancer effects of ASP on CRC. Network pharmacology analysis identified nine active components from ASP from the database based on oral bioavailability and drug similarity index, and 157 potential targets related to ASP were predicted. The PPI network identified tumor protein 53 (TP53), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), and AKT serine/threonine kinase 1 (AKT1) as key targets. GO analysis showed that ASP might act through response to wounding, membrane raft, and transcription factor binding. KEGG enrichment analysis revealed that ASP may affect CRC through the phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/AKT/mechanistic target of rapamycin kinase (mTOR) signaling pathway. In vitro, ASP inhibited cell proliferation, migration, and invasion of HCT116 and LOVO cells, and caused G0/G1 phase arrest and apoptosis in CRC cells. In vivo, ASP significantly inhibited the growth of CRC transplanted tumors in nude mice. Furthermore, pathway analysis confirmed that ASP could exert its therapeutic effects on CRC by regulating cell proliferation and survival through the PI3K/AKT/mTOR signaling pathway. This study is the first to report the potential role of ASP in the treatment of colorectal cancer.

Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: This meta-analysis was first conducted to evaluate the efficacy and safety of transplantation of mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM). METHODS: We systematically searched PubMed, ScienceDirect, Google Scholar, CNKI, EMBASE, Web of Science, MEDLINE, and the Cochrane Library for studies published from the establishment of the databases to November 2020. Two researchers independently screened the identified studies, based on inclusion and exclusion criteria. The combined standard mean difference (SMD) and 95% confidence interval (CI) of data from the included studies were calculated using fixed- or random-effects models. RESULTS: We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239 participants) to examine the efficacy of mesenchymal stem cells (MSCs) therapy in the treatment of diabetes mellitus. According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated group was significantly lower than it was at baseline (mean difference (MD) = -1.51, 95% CI -2.42 to -0.60, P = 0.001). The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the control group (SMD = 0.89, 95% CI 0.36 to 1.42, P = 0.001), and their insulin requirement was significantly lower than it was at baseline (SMD = -1.14, 95% CI -1.52 to -0.77, P < 0.00001). CONCLUSION: Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially T1DM, and no obvious adverse reactions.

Deletion of p37Ing1 in mice reveals a p53-independent role for Ing1 in the suppression of cell proliferation, apoptosis, and tumorigenesis.

ING proteins have been proposed to alter chromatin structure and gene transcription to regulate numerous aspects of cell physiology, including cell growth, senescence, stress response, apoptosis, and transformation. ING1, the founding member of the inhibitor of growth family, encodes p37(Ing1), a plant homeodomain (PHD) protein that interacts with the p53 tumor suppressor protein and seems to be a critical cofactor in p53-mediated regulation of cell growth and apoptosis. In this study, we have generated and analyzed p37(Ing1)-deficient mice and primary cells to further explore the role of Ing1 in the regulation of cell growth and p53 activity. The results show that endogenous levels of p37(Ing1) inhibit the proliferation of p53-wild-type and p53-deficient fibroblasts, and that p53 functions are unperturbed in p37(Ing1)-deficient cells. In addition, loss of p37(Ing1) induces Bax expression and increases DNA damage-induced apoptosis in primary cells and mice irrespective of p53 status. Finally, p37(Ing1) suppresses the formation of spontaneous follicular B-cell lymphomas in mice. These results indicate that p53 does not require p37(Ing1) to negatively regulate cell growth and offers genetic proof that Ing1 suppresses cell growth and tumorigenesis. Furthermore, these data reveal that p37(Ing1) can negatively regulate cell growth and apoptosis in a p53-independent manner.