XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular RNA, etc., which play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, we mainly summarized as followed: the role of exosome contents in cancer, focusing on proteins and noncoding RNA; the interaction between exosomes and tumor microenvironment; the mechanisms that epithelial-mesenchymal transition, invasion and migration of tumor affected by exosomes; and tumor suppression strategies based on exosomes. Finally, the application potential of exosomes in clinical tumor diagnosis and therapy is prospected, which providing theoretical supports for using exosomes to serve precise tumor treatment in the clinic.

/pdf/exosomes-key-players-in-cancer-and-potential-therapeutic-49qicrmv06.pdf

Exosomes: key players in cancer and potential therapeutic strategy.

Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC

Epigallocatechin-3-gallate (EGCG), an active compound of green tea and its role in diseases cure and prevention has been proven. Its role in diseases management can be attributed to its antioxidant and anti-inflammatory properties. The anti-cancer role of this green tea compound has been confirmed in various types of cancer and is still being under explored. EGCG has been proven to possess a chemopreventive effect through inhibition of carcinogenesis process such as initiation, promotion, and progression. In addition, this catechin has proven its role in cancer management through modulating various cell signaling pathways such as regulating proliferation, apoptosis, angiogenesis and killing of various types of cancer cells. The additive or synergistic effect of epigallocatechin with chemopreventive agents has been verified as it reduces the toxicities and enhances the anti-cancerous effects. Despite its effectiveness and safety, the implications of EGCG in cancer prevention is certainly still discussed due to a poor bioavailability. Several studies have shown the ability to overcome poor bioavailability through nanotechnology-based strategies such as encapsulation, liposome, micelles, nanoparticles and various other formulation. In this review, we encapsulate therapeutic implication of EGCG in cancer management and the mechanisms of action are discussed with an emphasis on human clinical trials.

/pdf/potential-therapeutic-targets-of-epigallocatechin-gallate-1d6556ickl.pdf

Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer.

抗氧化蛋白Prxs基因是新近发现的一类编码过氧化物酶的基因，广泛存在于原核生物和真核生物中，参与多种细胞活动的信号转导。文章综述了Prxs的结构及分型、定位和功能，并讨论了Prxs与运动的关系。

抗氧化蛋白（Peroxiredoxins）与运动

e16096 Background: Gastrointestinal cancers (colorectal cancer, gastric cancer and esophageal cancer) are the most prevalent malignant tumors in China, resulting in 975,537 new cases and 958,675 deaths in 2020. Currently, the gold standard for the early detection of these cancers remains to be gastrointestinal endoscopy. However, the invasiveness, low throughput and high cost of these procedures have prevented its wide acceptance by Chinese population. The objective of this study was to develop a liquid biopsy test based on the detection of multiple DNA methylation biomarkers (SpecGastro test) and evaluate its clinical performance for early detection of gastrointestinal cancers. Methods: Two hundred and eighty-two gastrointestinal cancer patients (98 colorectal cancers, 136 gastric cancers and 48 esophageal cancers) and 195 control subjects were included. Ten milliliters of peripheral blood was drawn and 3.5 mL plasma was separated for cell-free DNA extraction and bisulfite conversion. The converted DNA was subsequently examined by SpecGastro test, a multiplex qPCR assay that detected six methylation biomarkers and one internal control. Results: Overall sensitivity for SpecGastro test was 76.6% (95% CI: 71.1-81.3%) with a specificity of 89.2% (95% CI: 83.8-93.1%). Sensitivities for colorectal cancer, gastric cancer and esophageal cancer were 87.8% (95% CI: 79.2-93.2%), 69.9% (95% CI: 61.3-77.3%) and 72.9% (95% CI: 57.9-84.3%), respectively. A high AUC of 0.903 (95% CI: 0.873-0.928) indicated that SpecGastro test distinguished gastrointestinal cancer patients from control subjects with high accuracy. Conclusions: Our analysis demonstrated the utility of SpecGastro test to detect three types of gastrointestinal cancers with high sensitivity and specificity. These results supported the feasibility of this blood-based SpecGastro test as a complementary tool to the existing single-cancer early detection tests.

Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG. In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG. Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 μM), subsequently resulting in apoptosis. Based on the results of the in vivo study, size of xenografts treated with the combination of metformin and EGCG was smaller than other groups. Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2. Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway. Comparatively, the combination of EGCG and metformin showed little impact on normal lung epithelial BEAS-2B cells. Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.

/pdf/metformin-sensitizes-non-small-cell-lung-cancer-cells-to-an-5dl5fxoi1e.pdf

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.

Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. Radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (NSCLC) and is also used as a post-surgical treatment in lung cancer patients. Radioresistance is an important factor that limits the efficacy of radiotherapy for NSCLC patients. Increasing evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. In this study, we used miRNA microarray technology to identify serum miRNAs that were differentially expressed before and after radiotherapy in lung cancer patients. We further examined the biological function of miR-208a on cell viability, apoptotic death and cell cycle distribution in human lung cancer cells and explored the probable mechanism. Nine miRNAs, including miR-29b-3p, miR-200a-3p, and miR-126-3p were significantly down-regulated, whereas miR-208a was the only miRNA that was up-regulated in the serum of the patients after radiation treatment (P < 0.05). The expression of miR-208a could be induced by X-ray irradiation in lung cancer cells. Forced expression of miR-208a promoted cell proliferation and induced radioresistance via targeting p21 with a corresponding activation of the AKT/mTOR pathway in lung cancer cells, whereas down-regulation of miR-208a resulted in the opposite effects. In addition, down-regulation of miR-208a increased the percentage of cells undergoing apoptosis and inhibited the G1 phase arrest in NSCLC cells. Moreover, miR-208a from the serum exosome fraction of lung cancer patients could shuttle to A549 cells in a time-dependent manner, which was likely to contribute to the subsequent biological effects. The present study provides evidence that miR-208a can affect the proliferation and radiosensitivity of human lung cancer cells by targeting p21 and can be transported by exosomes. Thus, miR-208a may serve as a potential therapeutic target for lung cancer patients.

/pdf/radiation-induced-mir-208a-increases-the-proliferation-and-3td3mu1a2f.pdf

Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Peroxiredoxin 6 (PRDX6), a member of peroxidase superfamily, has a function of eliminating the reactive oxygen species (ROS), and participates in development of multiple diseases, including tumors. The purpose of this study was to investigate the expression of PRDX6 in normal and cancerous esophageal tissues and to characterize its role in ESCC progression. We found significantly higher expression of PRDX6 in ESCC tissues than in normal esophageal tissues or tumor-adjacent tissues and that the PRDX6 expression level was positively correlated with the proliferation-related markers. In ESCC cells, PRDX6 distribution was more pronounced in the nucleus region. PRDX6 overexpression by an adenovirus significantly promoted cell proliferation, migration and invasion in TE-1 and Eca-109 cells. Conversely, lentivirus-mediated knock-down of PRDX6 expression significantly reduced cell growth, colony formation and metastasis in ESCC cells. PRDX6 modulated the phosphorylation of Akt and Erk1/2, and the expression of MMP2. We also found that PRDX6 and Erk1/2 pathway were mutually regulated in ESCC cells. In addition, PRDX6 overexpression eliminated radiation-induced ROS and decreased consequent cell apoptosis, indicative of a role in radioresistance. Finally, the role of PRDX6 in promoting tumor growth was further confirmed in nude mice with ESCC xenografts. Taken together, we demonstrated that overexpression of PRDX6 promotes the progression of ESCC through Erk1/2, which provides a potential therapeutic target for human ESCC.

/pdf/overexpression-of-peroxiredoxin-6-prdx6-promotes-the-22xnrfktny.pdf

Overexpression of Peroxiredoxin 6 (PRDX6) Promotes the Aggressive Phenotypes of Esophageal Squamous Cell Carcinoma.

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Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.

Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells

Overexpression of Peroxiredoxin 6 (PRDX6) Promotes the Aggressive Phenotypes of Esophageal Squamous Cell Carcinoma.