Lipids in the Bone Marrow: An Evolving Perspective.

Bioinspired mineral hydrogels as nanocomposite scaffolds for the promotion of osteogenic marker expression and the induction of bone regeneration in osteoporosis.

Chronic kidney disease (CKD) was a major public health problem worldwide. Renal fibrosis, especially tubulointerstitial fibrosis, is final manifestation of CKD. Many studies have demonstrated that TGF-β/Smad signaling pathway plays a crucial role in renal fibrosis. Therefore, targeted inhibition of TGF-β/Smad signaling pathway can be used as a potential therapeutic measure for tubulointerstitial fibrosis. At present, a variety of targeting TGF-β1 and its downstream Smad proteins have attracted attention. Natural products used as potential therapeutic strategies for tubulointerstitial fibrosis have the characteristics of acting on multiple targets by multiple components and few side effects. With the continuous research and technique development, more and more molecular mechanisms of natural products have been revealed, and there are many natural products that inhibited tubulointerstitial fibrosis via TGF-β/Smad signaling pathway. This review summarized the role of TGF-β/Smad signaling pathway in tubulointerstitial fibrosis and natural products against tubulointerstitial fibrosis by targeting TGF-β/Smad signaling pathway. Additionally, many challenges and opportunities are presented for inhibiting renal fibrosis in the future.

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TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis

Icariin and its metabolites regulate lipid metabolism: From effects to molecular mechanisms

Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis: The Cardiovascular Risk in Young Finns Study.

Osteoporosis, characterized by bone mass reduction and increased fractures, has become a global health problem that seriously affects the health of people, especially postmenopausal women; however, the current pathogenesis of postmenopausal osteoporosis (PMOP) has not been thoroughly elucidated to date. In this study, bilateral ovariectomy was performed to establish an OVX mouse model of osteoporosis. UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics were used to analyze the femur tissue of osteoporosis mice. We found that 11 polar metabolites and 93 lipid metabolites were significantly changed and were involved in amino acid metabolism, nucleotide metabolism and lipid metabolism. Among the lipids, fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols showed robust changes. These results revealed that several metabolic disorders caused by changes in the hormone levels in OVX, especially disordered lipid metabolism, are closely related to the imbalance between bone resorption and formation and may underlie the development of PMOP. The data generated via lipidomics and metabolomics presented in this study shows good applicability and wide coverage in the construction of the metabolic profile of bone tissue. Therefore, this approach may provide the pathway focusing and data support at the metabolite level for the in-depth mechanism of PMOP.

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Integrative Bone Metabolomics-Lipidomics Strategy for Pathological Mechanism of Postmenopausal Osteoporosis Mouse Model.

Nephrolithiasis is a major public health problem worldwide and Fu-Fang-Jin-Qian-Cao granules (FFJQC) is a traditional Chinese herbal formula that is used to treat nephrolithiasis. The main componen...

Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-β/smad pathway.

Background Nephrolithiasis is a systemic metabolic disease with a high prevalence worldwide and is closely related to lipid-mediated oxidative stress and inflammation. Orthosiphon stamineus Benth. (OS) is a traditional medicinal herb mainly containing flavonoids, caffeic acid derivatives, and terpenoids, which has the effect of treating urinary stones. However, the active ingredients of OS for the treatment of kidney stones and their regulatory mechanisms remain unknown. As a powerful antioxidant, flavonoids from herbs can mitigate calcium oxalate stone formation by scavenging radical. Thus, this work focused on EtOAc extract of OS (EEOS, mainly flavonoids) and aimed to reveal the potential intrinsic mechanism of EEOS in the treatment of kidney stones disease. Methods Firstly, 75% ethanol extract of OS was further extracted with EtOAc to obtain EtOAc extract containing 88.82% flavonoids. Secondly, the extract was subjected to component analysis and used in animal experiments. Then, an untargeted lipidomics based on ultrahigh performance liquid chromatography coupled with TripleTOF 5600 mass spectrometer (UPLC-QTOF-MS) was performed to test the lipid changes of kidneys in the control group, model group and EEOS treatment groups. Finally, multivariate statistical analysis was used to identify differences between the lipid profiles of mice in the model group and the EEOS group. Results Fifty-one lipid metabolites were significantly different between the mice in the model group and the EEOS intervention group, including glycerophosphocholines, glycerophosphoethanolamines, glycerophosphoinositols, and glycerophosphoglycerols. And the composition of glycerophospholipids-esterified ω-3 polyunsaturated fatty acids and glycerophospholipid subclasses in the kidneys of the EEOS group significantly changed compared to model group. Conclusions The EEOS can inhibit the stones formation by improving oxidative stress and inflammation mediated by glycerophospholipid metabolism. This study reveals the potential mechanism of EEOS for kidney stones treatment at the lipid molecule level, providing a new direction for further study of the efficacy of OS.

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Lipidomics Reveals the Therapeutic Effects of EtOAc Extract of Orthosiphon stamineus Benth. on Nephrolithiasis.

A representative congener of polybrominated diphenyl ethers in the environment, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrations of BDE-47 for six weeks. Histopathological observations showed that BDE-47 induced inflammatory reactions and damaged the testes. By conducting an integrated proteomic and metabolomic analysis coupled with a bioinformatic analysis using ingenuity pathway analysis (IPA) methods, we found that BDE-47 mainly affected the molecules involved in free radical scavenging, cell death and survival, neurological disease, and inflammatory response. IPA canonical pathways showed inflammatory and apoptosis pathways, including hepatic fibrosis/hepatic stellate cell activation, the GP6 signaling pathway, tight junction signaling, acute phase response signaling, LXR/RXR activation, unfolded protein response, and FXR/RXR activation, which are related to male reproductive toxicity. Key transcriptional regulator networks were activated via a focus on upstream regulator analysis. The expression of MYC and Clu as the core transcriptional factor and targeted protein, respectively, was verified. It is further proposed that MYC may contribute to the etiology of male reproductive toxicity. These findings will improve our understanding of the mechanisms responsible for BDE-47-induced male reproductive toxicity, which may promote the discovery of useful biomarkers indicative of BDE-47 exposure.

https://www.mdpi.com/2218-273X/11/6/821/pdf

Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice.

The invention relates to a method for efficient synthesis of Stylissatin A natural cyclo-heptapeptide. The method mainly comprises the steps of 1, analysis of a Stylissatin A natural cyclo-heptapeptide retrosynthesis route; 2, solid-phase synthesis of linear chain peptide 6; 3, cyclization of linear chain peptide 6; 4, efficient liquid-phase separation of the product cyclopeptide. The method has the advantages that synthesis is easy and yield is high. The method can overcome the defect of small natural extraction amount and provides a material basis for further activity study.

Dong Xin

Papers

Integrative Bone Metabolomics-Lipidomics Strategy for Pathological Mechanism of Postmenopausal Osteoporosis Mouse Model.

Fu-Fang-Jin-Qian-Cao herbal granules protect against the calcium oxalate-induced renal EMT by inhibiting the TGF-β/smad pathway.

Lipidomics Reveals the Therapeutic Effects of EtOAc Extract of Orthosiphon stamineus Benth. on Nephrolithiasis.

Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice.

Method for efficient synthesis of Stylissatin A natural cyclo-heptapeptide