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Communication between osteoblasts and endothelial cells (ECs) is essential for bone turnover, but the molecular mechanisms of such communication are not well defined. Here we identify Cxcl9 as an angiostatic factor secreted by osteoblasts in the bone marrow microenvironment. We show that Cxcl9 produced by osteoblasts interacts with vascular endothelial growth factor and prevents its binding to ECs and osteoblasts, thus abrogating angiogenesis and osteogenesis both in mouse bone and in vitro . The mechanistic target of rapamycin complex 1 activates Cxcl9 expression by transcriptional upregulation of STAT1 and increases binding of STAT1 to the Cxcl9 promoter in osteoblasts. These findings reveal the essential role of osteoblast-produced Cxcl9 in angiogenesis and osteogenesis in bone, and Cxcl9 can be targeted to elevate bone angiogenesis and prevent bone loss-related diseases. Bone development and vascularization are coupled events that share many molecular mechanisms. Here the authors identify osteoblast-secreted Cxcl9 as an inhibitory regulator of angiogenesis and osteogenesis, and show that mTORC1 signaling and STAT1 are critical upstream mediators of the cytokine expression.

Mitochondrial dyshomeostasis provokes the onset of metabolic dysfunction‐associated steatotic liver disease (MASLD) although its precise involvement in particular mitophagy in MASLD remains elusive. This work evaluated the role of casein kinase 2α (CK2α) and FUNDC1 in high‐fat diet (HFD)‐evoked MASLD. WT and CK2α deletion (CK2α‐/‐) mice were subjected to low fat or HFD for 20 weeks. Global metabolism, AST, ALT, cholesterol, triglycerides, hepatic steatosis, fibrosis, inflammation, mitochondrial injury, mitophagy and ferroptosis were examined. Bioinformatics analysis enriched mitochondria‐related pathways in MASLD. Hepatic CK2α and FUNDC1 were upregulated and downregulated, respectively, in MASLD patients and HFD‐fed mice. HFD led to adiposity, hepatomegaly, hepatic steatosis, fibrosis, inflammation, ferroptosis, mitochondrial injury, elevated hepatic tissue Fe2+, FAS, CHREBP, SREBP1, PGC1α, PPARα, PPARγ, SCD1, PEPCK, G6Pase, and DGAT1 as well as downregulated FUNDC1, GPx4, SLC7A11 and NCOA4, the effects (except for NCOA4) were nullified by CK2α deletion. FUNDC1 deletion nullified CK2α deletion‐evoked benefit on hepatic ferroptosis and lipid enzymes. In vitro study using palmitic acid indicated an obligatory role for CK2α, FUNDC1 and ferroptosis in hepatocyte steatosis. Collectively, our results demonstrated that CK2α activation by HFD serves as a trigger for mitochondrial damage, hepatic injury, and pathogenesis of MASLD through FUNDC1 disruption and ferroptosis. Schematic graph exhibiting possible mechanism(s) for the role of CK2α and FUNDC1 in high fat diet‐induced hepatic steatosis. Long‐term high fat diet insult dampens FUNDC1‐mediated mitophagy through upregulation of CK2α, prompting disturbed lipid metabolism and lipid accumulation due to compromised mitophagy. Lipotoxicity subsequently promotes lipotoxic ferroptosis, imperiling hepatic steatosis.

Abstract Background Shenzhuo Formula (SZF), a modified Didang Tang, is used for diabetic kidney disease (DKD), though high-quality evidence is limited. Methods In a randomized, double-blind, double-dummy, active-controlled, multicenter trial, irbesartan (IRB) was the control. A Bayesian model assessed efficacy. Mechanistic studies included Olink inflammation proteomics, single-cell RNA sequencing (scRNA-seq) of KK-Ay mouse kidneys, and in vivo experiments. Results A total of 120 DKD patients with macroalbuminuria were randomized (SZF n = 57, IRB n = 63). At 24 weeks, 24 h urinary total protein change was −0.03 (−0.24 to 0.18) g/24 h in the SZF group and 0.08 (−0.30 to 0.14) g/24 h in the IRB group (P = 0.61). Estimated glomerular filtration rate improved with SZF by 5.91 (1.80 to 10.01) mL/min/1.73m² but declined with IRB by −1.67 (−5.18 to 1.84) mL/min/1.73m² (P < 0.01). Serum creatinine decreased with SZF by −5.15 (−9.73 to −0.56) μmol/L but increased with IRB by 3.39 (−0.84 to 7.61) μmol/L (P < 0.01). Traditional Chinese medicine syndrome response was higher with SZF (89.47% vs. 63.49%, P < 0.01). Safety and metabolic parameters were comparable. Bayesian analysis favored SZF for renal benefit. Mechanistically, SZF downregulated CX3CL1 in endothelial cells and MCP-1 in mesangial and tubular cells, suggesting anti-inflammatory effects restoring endothelial function and attenuating fibrosis. Conclusions SZF matched IRB in proteinuria reduction but was superior in preserving renal function and improving traditional Chinese medicine symptoms in DKD, with good safety. Benefits may involve suppression of CX3CL1/MCP-1-mediated inflammation.

Objective. Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results. Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD=−0.73; 95% CI (−0.97, −0.51)), FPG (MD=−0.86, 95% CI (−1.10, −0.62)), and 2hPG (MD=−1.26, 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS (MD=−2.05, 95% CI (−2.62, −1.48)), HOMA-IR (MD=−0.71, 95% CI (−1.03, −0.39)), and BMI (MD=−1.07, 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD=−0.5, 95% CI (−0.61, −0.39)), TC (MD=0.64, 95% CI (−0.78, −0.49)), and LDL (MD=0.86, 95% CI (−1.06, −0.65)) and the upregulation of HDL (MD=0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

In Chinese medicine, diabetes belongs to the category of “Xiaoke disease (disease with symptoms of frequent drinking and urination)”; in the traditional sense, its pathogenesis is “Yin deficiency and dryness-heat.” However, over time, changes in the social environment and lifestyle have also changed the use of traditional Chinese medicine (TCM) in diabetes. In this study, we performed diabetes syndrome differentiation using TCM according to evidence-based medicine and expert consensus opinion.

Diabetes mellitus has been a global pandemic. Traditional Chinese Medicine has been used on diabetes mellitus for thousands of years and the modern Chinese medicine studies have found a curative effect of herbal medicine with bitter flavor and cold property on diabetes. This review will introduce the theory summary of flavor and property in TCM, argument basis, the evidences from clinical trails and animal experiments, the possible antidiabetic mechanisms, and advantages on lowering glucose of herbal medicines with bitter flavor and cold property and take rhizome, Chinese rhubarb, and Momordica charantia, the three herbal medicines with bitter flavor and cold property, as examples to illustrate the exact antidiabetic effect. It is hoped that this review can provide some ideas and inspiration for the treatment of diabetes with herbal medicine.

The rapidly increasing incidence of diabetes mellitus (DM) is becoming a major public health issue. As one of the important parts in complementary and alternative therapies, traditional Chinese medicine (TCM) is promising in treating DM. In this review, we summarize new thoughts on treating DM that aim to improve the clinical efficacy of TCM from the perspectives of principle, methods, formula, herbs, and doses. Our approach is as follows: principle: we use a combination of symptoms, syndromes, and diseases as a new mode for treating diabetes; methods: emphasizing heat-clearing in the early and middle stage of T2DM and invigorating blood circulation throughout the whole process of T2DM are two innovative methods to treat T2DM; formulas and herbs: choosing formulas and herbs based on the combination of TCM theory and current medicine. We will emphasize four strategies to help doctors choose formulas and herbs, including treatment based on syndrome differentiation, choosing herbs of bitter and sour flavors to counteract sweet flavor, choosing formulas and herbs aimed at main symptoms, and using modern pharmacological achievements in clinical practice; dose: reasonable drug dose plays an important role in the treatment of DM and a close relationship exists between dose and clinical efficacy.

PurposeThe purpose of this study is to investigate e-commerce as a new means to ensure that the urban demand for food can be met during the coronavirus disease 2019 (COVID-19) outbreak. Because a number of COVID-19 e-commerce models have emerged, this paper discusses whether and (if so) why and how e-commerce can ensure the food supply for urban residents if social distancing becomes a norm and the transport and logistics systems are hindered.Design/methodology/approachThis study used qualitative research methods following the lack of empirical data. The authors referred to relevant literature, statistical data and official reports and comprehensively described the importance of e-commerce in ensuring the safety of food supply to Chinese urban residents under the impact of the epidemic. Corresponding to the traditional case study, this study presented a Chinese case on ensuring food supply through e-commerce during an epidemic.FindingsThe authors found that three e-commerce models played a substantial role in preventing the spread of the epidemic and ensuring the food supply for urban residents. The nationwide e-commerce platforms under market leadership played their roles by relying on the sound infrastructure of large cities and its logistics system was vulnerable to the epidemic. In the worst-affected areas, particularly in closed and isolated communities, the local e-commerce model was the primary model, supplemented by the unofficial e-commerce model based on social relations. Through online booking, centralized procurement and community distribution, the risk of cross infection could be effectively reduced and the food demand could be effectively satisfied. The theoretical explanation further verifies that, apart from e-commerce, a governance system that integrates the government, e-commerce platform, community streets and the unofficial guanxi also impels the success of these models.Originality/valueLessons from China are drawn for other countries struggling to deliver food to those in need under COVID-19. The study not only provides a solution that will ensure constant food supply to urban residents under the COVID-19 epidemic but also provides some reference for the maintenance of the food system of urban residents under the impact of a globalization-related crisis in future.

The in-depth development of generative adversarial networks in the field of specific application tasks, the single image super-resolution problem has been widely studied. We proposed a novel reconstruction model using generative adversarial network for single image super-resolution reconstruction task. Our model directly learns an end-to-end mapping between the low and high-resolution images. The mapping is represented as a generative adversarial network that takes the low-resolution images as the input and outputs the high-resolution one. We further confirmed that the spectral normalization and attention method is exceedingly effective for the training of stably generating adversarial networks. We use a more lightweight external attention method in the network to accelerate the speed of global structure reconstruction. It is different from the previous image super-resolution task. Our model implements multi-scale joint training and optimizes all layers. We explore different networks structures and parameter settings to achieve trade-offs between performance and speed. Quantitative indexes and qualitative results show that our proposed method achieves comparable performance with the state-of-the-art supervised models.