Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure.

BACKGROUND: In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). METHODS: A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 < 2.3pg/mL, n = 168) and non-LT3S group (FT3 ≥ 2.3pg/mL, n = 426). RESULTS: In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. CONCLUSIONS: In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

[Research Progress on the Genomics of Taenia solium and Candidate Vaccines for Cysticercosis].

Research on cysticercosis has been stimulated by the rapid development of genomics, proteomics and bioinformatics and the emergence of molecular biological and immunological technologies. In this review, we attempt to discuss the research development on genomics of Taenia solium and candidate vaccines and antigens for cysticercosis. This will provide a new perspective for studying genomics of Taenia solium and for cysticercosis prevention and treatment, and provide a wealth of informative data for the development of novel and highly efficient vaccines against cysticercosis or diagnostic antigen molecules for cysticercosis.

The BRAFV600E mutation maintains the aggressiveness of papillary thyroid cancers requiring downregulation of primary cilia.

Although disorders of primary cilia (PCs) were first reported in human papillary thyroid cancer (PTC) tissues in 1987, their precise role in PTC remains unclear. PCs sense the thyroid follicle colloid environment and act as a cell signaling hub. The present study investigated whether PCs are needed for BRAFV600E-driven PTC. We assessed whether BRAFV600E protein expression correlates with papillary histological architecture and clinicopathological features of PTC. We found that expression of ciliary intraflagellar transport 88 (IFT88) and PC formation were reduced in BRAFV600E-driven PTCs and that loss of cilia may be associated with lymph node metastasis. In PTC cells, the BRAFV600E mutation maintained the aggressiveness of PTC, which was partially related to loss of PCs. Our work confirms that BRAFV600E mutation-driven PC downregulation contributes to maintaining the aggressiveness of PTCs and that manipulating PC can potentially reduce the adverse incidence of PTC in a range of conditions.

Codonopsis pilosula polysaccharides promote osteogenic differentiation and inhibit lipogenic differentiation of rat bone marrow stem cells by activating ß-catenin.

Aberrant bone marrow mesenchymal stem cell (BMSC) lineage differentiation leads to osteoporosis. Codonopsis pilosula polysaccharides (CPPs) have been widely used in traditional Chinese medicines, due to their multiple pharmacological actions. However, little is known regarding their effects on BMSC differentiation. This study aimed to identify the effects and mechanisms of CPPs on osteogenic and adipogenic differentiation in rat BMSCs. An osteoporosis model was established in Sprague-Dawley (SD) rats through bilateral ovariectomy (OVX), and be applied to observe the effect of CPPs on osteoporosis in vivo. The ability of CPPs to affect rBMSC proliferation was determined using the CCK-8 assay, and the osteogenic differentiation of rBMSCs measured by ALP and Alizarin Red S staining. The adipogenic differentiation of rBMSCs was measured by Oil Red O staining. The mRNA and protein levels related to osteogenesis and adipogenic differentiation of rBMSCs were measured using qRT-PCR and western blotting, respectively. Cellular immunofluorescence was used to detect cytokine expression and localisation in rBMSCs. We observed that CPPs ameliorated bone loss in OVX rats. CPPs considerably enhanced osteogenic differentiation by increasing ALP activity and the prevalence of mineralised nodules and promoting the mRNA and protein expression of osteogenic differentiation markers (RUNX2, COL I, ALP, and OPN). Furthermore, it inhibited the accumulation of lipid vesicles in the cytoplasm and the mRNA and protein expression levels of adipogenic differentiation markers (PPARγ and C/EBPα) in a concentration-dependent manner. Meanwhile, CPPs notably increased the mRNA and protein expression of ß-catenin, the core protein of the Wnt/ß-catenin signaling pathway, in a concentration-dependent manner. Adding DKK1, a mature inhibitor of the Wnt/ß-catenin signaling pathway, partially suppressed CPP-stimulated ß-catenin activation, and reversed the acceleration of osteogenic differentiation and the inhibition of lipogenic differentiation. Our observations demonstrated CPPs ameliorate bone loss in OVX rats in vivo, and favour osteogenic differentiation while inhibit adipogenic differentiation of rBMSCs in vitro. The findings suggested that CPPs could serve as functional foods for bone health, and have great potential for the prevention and treatment of osteoporosis.

The association of obesity with thyroid carcinoma risk.

BACKGROUND: The prevalence of obesity and an increased incidence of thyroid carcinoma (TC) threaten public health in parallel on a global scale. Sufficient evidence supports excess body fatness in thyroid carcinogenesis, and the role and anthropometric markers of obesity have been causally associated with the rising risk of TC. METHODS: A literature search was conducted in PubMed. Studies focused on the effect of obesity in TC. RESULTS: This review mainly discusses the global incidence and prevalence of obesity-related TC. We also review the role of obesity in TC and potential clinical strategies for obesity-related TC. CONCLUSIONS: Excess body fatness in early life and TC survival initiate adverse effects later in life.

Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?

Target identification is essential for developing novel therapeutic strategies in diseases. Thioredoxin-interacting protein (TXNIP), also known as thioredoxin-binding protein-2, is a member of the α-arrestin protein family and is regulated by several cellular stress factors. TXNIP overexpression coupled with thioredoxin inhibits its antioxidant functions, thereby increasing oxidative stress. TXNIP is directly involved in inflammatory activation by interacting with Nod-like receptor protein 3 inflammasome. Bone metabolic disorders are associated with aging, oxidative stress, and inflammation. They are characterized by an imbalance between bone formation involving osteoblasts and bone resorption by osteoclasts, and by chondrocyte destruction. The role of TXNIP in bone metabolic diseases has been extensively investigated. Here, we discuss the roles of TXNIP in the regulatory mechanisms of transcription and protein levels and summarize its involvement in bone metabolic disorders such as osteoporosis, osteoarthritis, and rheumatoid arthritis. TXNIP is expressed in osteoblasts, osteoclasts, and chondrocytes and affects the differentiation and functioning of skeletal cells through both redox-dependent and -independent regulatory mechanisms. Therefore, TXNIP is a potential regulatory and functional factor in bone metabolism and a possible new target for the treatment of bone metabolism-related diseases.

Metabolic (Dysfunction)-Associated Fatty Liver Disease in Chinese Patients with Type 2 Diabetes from a Subcenter of the National Metabolic Management Center.

BACKGROUND: Few studies have investigated the epidemiological metabolic (dysfunction) associated with fatty liver disease (MAFLD) in China, especially among those with type 2 diabetes. METHODS: We recruited 3553 patients aged 18-75 years with type 2 diabetes who underwent abdominal ultrasound and serum biochemical analyses. Patient information including demographic and anthropometric parameters was also collected. RESULTS: Overall, 63.2% of type 2 diabetic patients had MAFLD. Among the MAFLD patients, the proportions of lean, nonobese, and obese MAFLD were 23.1%, 75.7%, and 24.3%, respectively, and the percentage of previously undiagnosed MAFLD was 42.2%. MAFLD patients were younger, had shorter diabetic duration, and had greater BMI, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting insulin, postprandial insulin, total cholesterol, and insulin resistance levels (HOMA-IR and TyG index). Liver fibrosis diagnostic panels revealed that the proportions of elevated AST (≥40 U/L) and ALT (≥40 U/L) were 7.3% and 18.5%, respectively. The distributions of AST-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) index, and nonalcoholic fatty liver disease fibrosis score (NFS) per stage were as follows: APRI-low 55.1%, indeterminate 35.3%, and high 9.5%; FIB-4-low 48.2%, indeterminate 45.3%, and high 6.5%; and NFS-low 15.0%, indeterminate 70.0%, and high 13.0%. CONCLUSIONS: MAFLD is a very common condition and generally had greater frequency of metabolic characteristics among type 2 diabetics in China. Many MAFLD patients were in the "indeterminate" or "high" stage when APRI, FIB-4, and NFS were assessed. Assessment of MAFLD should be included in the management of type 2 diabetes.

Ultrafiltration Extract of Radix Angelica Sinensis and Radix Hedysari Attenuates Risk of Low-Dose X-Ray Radiation-Induced Myocardial Fibrosis In Vitro.

The risk of radiation-induced heart damage (RIHD) is a growing concern since recent advances in radiation therapy (RT) for cancer treatments have significantly improved the number of survivors. Radiation-induced myocardial fibrosis (RIMF) is the final pathological condition of RIHD and main change leading to serious cardiovascular complications following RT. The aim of this study was to investigate the effect of ultrafiltration extract of Radix Angelica Sinensis and Radix Hedysari (RAS-RH) on the proliferation, apoptosis, and reactive oxygen species (ROS) of cardiac fibroblasts after X-irradiation in vitro. The RAS-RH extract was from the Danggui Buxue decoction (DBD) in TCM. Primary cardiac fibroblasts were irradiated with 1 Gy X-ray to evaluate the effect of RAS-RH on the expression levels of cell proliferation, apoptosis, ROS, and fibrotic molecules. Our data demonstrated that X-irradiation at 1 Gy resulted in the proliferation of cardiac fibroblasts; RAS-RH attenuated the myocardial fibrosis. Furthermore, X-ray radiation reduced the apoptosis of cardiac fibroblasts; RAS-RH accelerated the apoptosis of these cells after irradiation. In addition, the damage driven by ROS in primary cardiac fibroblasts after irradiation was weakened by RAS-RH and the expression of TGF-ß1, Col1, and α-SMA increased after irradiation; RAS-RH decreased the expression of these makers. Overall, these data indicate that low-dose X-ray irradiation boosts myocardial fibrosis, and the effect of RAS-RH protects against fibrosis via attenuating the proliferation and accelerating the apoptosis of myocardial fibroblasts after X-irradiation.

NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1ß and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1ß and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. In vivo and in vitro experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis.

The Role of Primary Cilia in Thyroid Cancer: From Basic Research to Clinical Applications.

Primary cilia (PC) are microtubule-based organelles that are present on nearly all thyroid follicle cells and play an important role in physiological development and in maintaining the dynamic homeostasis of thyroid follicles. PC are generally lost in many thyroid cancers (TCs), and this loss has been linked to the malignant transformation of thyrocytes, which is regulated by PC-mediated signaling reciprocity between the stroma and cancer cells. Restoring PC on TC cells is a possible promising therapeutic strategy, and the therapeutic response and prognosis of TC are associated with the presence or absence of PC. This review mainly discusses the role of PC in the normal thyroid and TC as well as their potential clinical utility.

MiR-192-5p inhibits proliferation, migration, and invasion in papillary thyroid carcinoma cells by regulation of SH3RF3.

BACKGROUND: The decreased level of miR-192-5p has been reported in several kinds of cancers, including bladder, colon, ovarian, and non-small cell lung cancer. However, the expression and function of miR-192-5p in papillary thyroid carcinoma/cancer (PTC) remains unknown. OBJECTIVE: The present study aimed to explore the function and underlying mechanism of miR-192-5p in PTC development. METHODS: PTC tissues and relative normal controls from PTC patients were collected. qRT-PCR analysis was performed to measure miR-192-5p and SH3RF3 mRNA level in PTC tissues and cell lines. CCK-8 method and FCM assay were used to test cell proliferation and apoptosis in TPC-1 cells, respectively. The abilities of cell migration and invasion were detected by wound healing and transwell assays, respectively. The protein expression was evaluated by Western blot. The interaction between miR-192-5p and Src homology 3 (SH3) domain containing ring finger 3 (SH3RF3) were confirmed by dual-luciferase reporter assay. RESULTS: MiR-192-5p level was obviously decreased in PTC tissues and cell lines. Overexpression of miR-192-5p suppressed proliferation, migration, invasion, and EMT process, while induced apoptosis in TPC-1 cells. In addition, miR-192-5p negatively modulated SH3RF3 expression by binding to its 3'-untranslated region (3'UTR). Silencing SH3RF3 inhibited the migration, invasion, and EMT of TPC-1 cells. In the meantime, matrine, an alkaloid extracted from herb, exerted its anti-cancer effects in PTC cells dependent on increase in miR-192-5p expression and decrease in SH3RF3 expression. CONCLUSION: We firstly declared that miR-192-5p played a tumor suppressive role in PTC via targeting SH3RF3. Moreover, matrine exerted its anti-cancer effects in PTC via regulating miR-192-5p/SH3RF3 pathway.

CircRNA: A novel potential strategy to treat thyroid cancer (Review).

Thyroid cancer (TC) is the most common type of endocrine cancer. Over the last 50 years, the global incidence of TC has been increasing. The survival rate of TC is higher than that of most other types of cancer, but it depends on numerous factors, including the specific type of TC and stage of the disease. Circular RNAs (circRNAs) are a new class of long noncoding RNA with a closed loop structure that have a critical role in the complex gene regulatory network that controls the emergence of TC. The most important function of circRNAs is their ability to specifically bind to microRNAs. In addition, the biological functions of circRNAs also include interactions with proteins, regulation of the transcription of genes and acting as translation templates. Based on the characteristics of circRNAs, they have been identified as potential biomarkers for the diagnosis of tumors. In the present review, the function and significance of circRNAs and their potential clinical implications for TC were summarized. Furthermore, possible treatment approaches involving the use of mesenchymal stem cells (MSCs) and exosomes derived from MSCs as carriers to load and transport circRNAs were discussed.

miRNA, lncRNA and circRNA: Targeted Molecules Full of Therapeutic Prospects in the Development of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common diabetic complication and the main cause of blindness worldwide, which seriously affects the quality of life of patients. Studies have shown that noncoding RNA (ncRNA) has distinct differentiated expression in DR and plays an important role in the occurrence and development of DR. ncRNAs represented by microRNAs (miRNAs), lncRNAs (lncRNAs), and circRNAs (circRNAs) have been shown to be widely involved in the regulation of gene expression and affect multiple biological processes of retinopathy. This article will review three RNAs related to the occurrence and development of DR on the basis of previous studies (especially their effects on retinal microangiopathy, retinal pigment epithelial cells, and retinal nerve cells) and discuss their underlying mechanisms and connections. Overall, this review will help us better understand the role of ncRNAs in the occurrence and development of DR and provide ideas for exploring potential therapeutic directions and targets.

GDF15 Promotes Cardiac Fibrosis and Proliferation of Cardiac Fibroblasts via the MAPK/ERK1/2 Pathway after Irradiation in Rats.

Ionizing radiation exposure is associated with a risk of cardiac fibrosis; however, the underlying molecular mechanism remains unclear. Growth/differentiation factor-15 (GDF15), a fibroblast factor, is a divergent member of the transforming growth factor ß superfamily. Next-generation sequencing analyses has revealed that Gdf15 is increased in cardiac fibroblasts during radiation-induced fibrosis. However, the role of Gdf15 in cardiac fibrosis remains unclear. In this study, we demonstrated that the upregulated expression of GDF15 in newborn rat cardiac fibroblasts and adult rats after irradiation could induce fibrosis, which was confirmed by the increased cell proliferation rate and the increased expression of fibrosis markers (Col1α and αSMA) in newborn rat cardiac fibroblasts after transfection with Gdf15 in vitro. Conversely, the downregulation of GDF15 inhibited cardiac fibrosis, as confirmed by G2/M-cell cycle arrest, suppression of cell proliferation, and low levels of Col1α and αSMA expression. We also found that suppressing the expression of Gdf15 in cardiac fibroblasts could lead to a decrease in CDK1 and inhibit phosphorylation of ERK1/2. Thus, GDF15 might promote cardiac fibroblast fibrosis through the MAPK/ERK1/2 pathway and thus contribute to the pathogenesis of radiation-induced heart disease.

Radix Angelica Sinensis and Radix Hedysari Ultrafiltration Extract Protects against X-Irradiation-Induced Cardiac Fibrosis in Rats.

Radiation-induced myocardial fibrosis (RIMF) is the main pathological change associated with radiation-induced heart toxicity after radiation therapy in patients with thoracic tumors. There is an antifibrosis effect of Radix Angelica Sinensis and Radix Hedysari (RAS-RH) ultrafiltration extract from Danggui Buxue decoction (DBD) in X-irradiation-induced rat myocardial fibrosis, and this study aimed to investigate whether that effect correlated with apoptosis and oxidative stress damage in primary rat cardiac fibroblasts; further, the potential mechanisms were also explored. In this study, we first found that the RAS-RH antifibrosis effect was associated with the upregulation of microRNA-200a and the downregulation of TGF-ß1/smad3 and COL1α. In addition, we also found that the antifibrosis effect of RAS-RH was related to the induction of apoptosis in primary rat cardiac fibroblasts and to the prevention of damage caused by reactive oxygen species (ROS). Interestingly, primary rat cardiac fibroblasts exposed to X-ray radiation underwent apoptosis less frequently in the absence of RAS-RH. Therefore, RAS-RH has the ability to protect against fibrosis, which could be occurring through the induction of apoptosis and the resistance to oxidative stress in rats with X-irradiation-induced myocardial fibrosis; thus, in a model of RIMF, RAS-RH acts against X-irradiation-induced cardiac toxicity.

15-PGDH Expression in Gastric Cancer: A Potential Role in Anti-Tumor Immunity.

INTRODUCTION: Host immunity plays a vital role in tumorigenesis, including in tumor invasion and metastasis. However, the precise underlying mechanism remains to be explored. The enzyme 15-PGDH, which plays a key role in prostaglandin degradation, is a critical inflammatory mediator in gastric cancer (GC) tumorigenesis. MATERIALS AND METHODS: Immunohistochemistry was performed to determine 15-PGDH expression in GC and the corresponding adjacent non-neoplastic tissues (n=92). RESULTS: The expression of 15-PGDH in GC tissues was significantly lower than that in paracancerous tissues (P<0.001) and found to correspond inversely with GC differentiation (P=0.043) and lymph node metastasis (P=0.046). In contrast, FOXP3 expression was increased in poorly differentiated GC tissues (P=0.001). Kaplan-Meier analysis revealed that GC patients with low expression of 15-PGDH (Log rank test, P=0.007) and high expression of FOXP3 (Log rank test, P=0.009) had shorter overall survival (OS) than those with high 15-PGDH and low FOXP3 expression. OS was also correlated with pathological tumor-node-metastasis stage (Log rank test, P=0.014). Furthermore, using Cox proportional hazard regression, 15-PGDH expression [hazard ratio (HR): 0.605 (0.440-0.833); P=0.002] was identified as an independent factor for OS. CONCLUSION: Our data suggest that 15-PGDH may contribute to anti-tumor immunity by regulating FOXP3+ Treg cells. The findings are useful for the identification of therapeutic targets for the management of GC.

miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts.

BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. METHODS: We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. RESULTS: DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation-the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation.

New therapeutic insights into radiation-induced myocardial fibrosis.

Radiation therapy (RT) for the treatment of thoracic tumors causes radiation-induced heart disease (RIHD). Radiation-induced myocardial fibrosis (RIMF) is both an acute and chronic stage of RIHD, depending on the specific pathology, and is thought to be a major risk factor for adverse myocardial remodeling and vascular changes. With the use of more three-dimensional conformal radiation regimens and early screenings and diagnoses for RIMF, the incidence of RIHD is declining, but it still must be carefully investigated to minimize the mortality and morbidity of patients with thoracic malignancies after RT treatment. Effective methods for preventing RIMF involve a decrease in the direct radiation dose in the heart, and early screening and diagnosis. Medications remain as a useful adjunct for preventing or treating RIMF. This review mainly discusses the cellular and molecular mechanisms underlying RIMF, and new therapeutic drugs that can potentially be developed from this knowledge.

The effects of Radix Angelica Sinensis and Radix Hedysari ultrafiltration extract on X-irradiation-induced myocardial fibrosis in rats.

Radix Angelica Sinensis and Radix Hedysari are traditional Chinese medicines that are used for preventing and treating various diseases. This study aimed to investigate the effect and possible underlying mechanisms of Radix Angelica Sinensis and Radix Hedysari ultrafiltration extract (RAS-RH) on X-irradiation-induced cardiac fibrosis in rats. Our data demonstrated that (a) a single dose of total body irradiation (TBI) at 8 Gy resulted in cardiac fibrosis, whereas the control hearts exhibited less collagen and fibrosis. RAS-RH mitigated these morphological injuries. (b) TBI resulted in an increase in the serum levels of transforming growth factor ß1 (TGF-ß1) and troponin-I (TnI). RAS-RH inhibited the release of TBI-induced serum TGF-ß1 and the TnI levels. (c) TBI inhibited the apoptosis of primary rat cardiac fibroblasts, whereas RAS-RH induced the apoptosis of primary rat cardiac fibroblasts after X- irradiation. (d) TBI resulted in an increase in the expression of osteopontin (OPN), c-fos, c-jun, miRNA-21 and collagen1α (COL1α) in primary rat cardiac fibroblasts, and RAS-RH mitigated the TBI-induced increased expression of OPN, c-jun, miRNA-21 and COL1α. In conclusion, these results demonstrate that RAS-RH exerts antifibrotic effects possibly through inducing the apoptosis of fibroblasts, inhibiting the release of serum TGF-ß1, reducing the levels of serum TnI and reducing the expression of OPN, c-jun, miRNA-21 and COL1α. Therefore, RAS-RH may potentially be developed as a medical countermeasure for the mitigation of radiation-induced myocardial fibrosis.