Thermo-reversible gelation of myofibrillar protein: Relationship between coiled-coil and thermal reversibility.

Thermo-reversible gel of myofibrillar protein (MP) can be made by tactics of elaborate deamidation using protein-glutaminase (PG), and this work aimed to disclose the link between thermally reversible gelation of MP and the coiled-coil (CC). Enzymatic deamidation fragmented myofibril filaments and triggered structural reassembly to create small-sized aggregates. The coiling and dissociation of CC structure in the myosin tails is the fundamental structural basis of the PG deamidated MP (DMP) in the dynamic evolution of reversible gelation. After specific inhibition of CC assembly by trifluoroethanol (TFE), the thermo-reversible gel ability of DMP was impaired, which confirmed that the dynamic assembly of CC with temperature response played a key role in the thermo-reversible gelation of DMP. The findings may broaden the molecular basis of natural CC reversible gelation and foster advances for the development of new muscle protein products.

Extracellular Non-Coding RNAs in Cardiovascular Diseases.

Cardiovascular diseases (CVDs) remain the world's leading cause of death despite the best available healthcare and therapy. Emerging as a key mediator of intercellular and inter-organ communication in CVD pathogenesis, extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed nano-sized vesicles released by virtually all cells, of which their RNA cargo, especially non-coding RNAs (ncRNA), has been increasingly recognized as a promising diagnostic and therapeutic target. Recent evidence shows that ncRNAs, such as small ncRNAs, circular RNAs, and long ncRNAs, can be selectively sorted into EVs or other non-vesicular carriers and modulate various biological processes in recipient cells. In this review, we summarize recent advances in the literature regarding the origin, extracellular carrier, and functional mechanisms of extracellular ncRNAs with a focus on small ncRNAs, circular RNAs, and long ncRNAs. The pathophysiological roles of extracellular ncRNAs in various CVDs, including atherosclerosis, ischemic heart diseases, hypertension, cardiac hypertrophy, and heart failure, are extensively discussed. We also provide an update on recent developments and challenges in using extracellular ncRNAs as biomarkers or therapeutical targets in these CVDs.

Myofibrillar protein can form a thermo-reversible gel through elaborate deamidation using protein-glutaminase.

BACKGROUND: Novel thermo-reversible hydrogels that undergo gelation in feedback to external stimuli have numerous applications in the food, biomedical, and functional materials fields. Muscle myofibrillar protein (MP) has long been known for thermally irreversible gelation. Once the reversible gelation of MP is achieved, its scope for research and application will expand. RESULTS: The work reported here achieved, for the first time, a thermo-reversible MP gelation by elaborate deamidation using protein glutaminase (PG). The protein concentration and PG reaction time within windows of 1.0-2.5% and 8 h or 12 h were observed to be vital for creating thermo-reversible gels. The gel strength increased with protein concentration. The gel displayed a perforated lamellar microstructure, which resulted in a high water-holding capacity. The rheological results revealed the thermo-reversibility of the gel was robust for up to five cycles of heating and cooling. The thermally reversible gelation is closely related to the reversible assembly between individual α-helix and helical coiled coil. Hydrophobic interactions proved to be predominantly involved in the formation and stabilization of the gel network structure. CONCLUSION: This work increases the scope of research into the thermo-responsive behavior of MP-based gel. It can foster advances in research into the applications of muscle proteins and into the use of PG as a novel ingredient in the food industry. © 2022 Society of Chemical Industry.

Disulfiram-loaded hollow copper sulfide nanoparticles show anti-tumor effects in preclinical models of colorectal cancer.

Colorectal cancer is one of the most common malignancies causing the majority of cancer-related deaths. There is an urgent need to develop new anticancer modalities. Recently, efforts have been made to turn clinically approved drugs into anticancer agents in specific tumor microenvironments via NPs. Disulfiram (DSF) as an effective copper (Cu2+)-dependent anti-tumour drug, which has been more widely used in antitumor research. Here, we constructed a novel therapeutic nanoplatforms, DSF@CuS, by encapsulating DSF in hollow CuS NPs to enable in situ chemoselective activation of DSF and hyperthermal amplified chemotherapy. The anticancer effect of DSF was enhanced by the thermal energy generated under NIR irradiation through the intrinsic photothermal conversion of CuS. As a result, significant apoptosis was induced in vitro, and tumor elimination was achieved in vivo. Collectively, DSF@CuS combined with photothermal therapy can significantly promote the apoptosis of CT26 colorectal cancer cells both in vitro and in vivo, providing a potential theoretical agent for the treatment of colorectal cancer.

ITF2357 induces cell cycle arrest and apoptosis of meningioma cells via the PI3K-Akt pathway.

As a type of central nervous system tumor, meningioma usually compresses the nerve center due to its local expansion, further causing neurological deficits. However, there are limited therapeutic approaches for meningiomas. ITF2357, a potent class I and II histone deacetylase inhibitor (HDACi), has been shown to inhibit cell proliferation, promote apoptosis, and block the cell cycle in various sarcoma cells, including glioblastoma and peripheral T-cell lymphoma. Here, we investigated the potential role of ITF2357 on meningioma cancer cells (IOMM-Lee cells). First, we demonstrated that the half-maximal inhibitory concentration (IC50) of ITF2357 was 1.842 µM by MTT assay. In addition, ITF2357 effectively inhibited the proliferation and colonization ability of IOMM-Lee cells. Flow cytometry analysis showed that ITF2357 induced G0/G1 and G2/M phase cell cycle arrest and cell apoptosis. Mechanically, the RNA sequencing data revealed that ITF2357 could affect the PI3K-Akt signaling pathway and the cell cycle progression. Furthermore, the expression levels of Akt, PI3K, p-Akt, and p-PI3K were determined by western blotting. Collectively, our data revealed that ITF2357 induces G0 G1 and G2/M phase arrest and apoptosis by inhibiting hyperactivation of the PI3K-Akt pathway, ultimately inhibiting cell viability and proliferation of meningioma cells, which developed a new approach to the treatment of meningioma.

Regulation and roles of RNA modifications in aging-related diseases.

With the aging of the global population, accumulating interest is focused on manipulating the fundamental aging-related signaling pathways to delay the physiological aging process and eventually slow or prevent the appearance or severity of multiple aging-related diseases. Recently, emerging evidence has shown that RNA modifications, which were historically considered infrastructural features of cellular RNAs, are dynamically regulated across most of the RNA species in cells and thereby critically involved in major biological processes, including cellular senescence and aging. In this review, we summarize the current knowledge about RNA modifications and provide a catalog of RNA modifications on different RNA species, including mRNAs, miRNAs, lncRNA, tRNAs, and rRNAs. Most importantly, we focus on the regulation and roles of these RNA modifications in aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, cataracts, osteoporosis, and fertility decline. This would be an important step toward a better understanding of fundamental aging mechanisms and thereby facilitating the development of novel diagnostics and therapeutics for aging-related diseases.

[Value of serum soluble interleukin-2R, interleukin-6 and C-reactive protein in the early diagnosis of Kawasaki disease].

OBJECTIVE: Immunovasculitis is a pathologic process of Kawasaki disease (KD) in the early stage and it is more likely to result from abnormal immunoactivation. It is thus speculated that the serum levels of some cytokines have changed before immunovasculitis occurs, suggesting the cytokines may be useful markers for the early diagnosis of KD. In this study, we measured the serum levels of soluble interleukin-2 receptors (sIL-2R), interleukin-6(IL-6) and high-sensitive C-reactive protein (hs-CRP) in patients with KD to evaluate the significance of these cytokines in the early diagnosis of KD. METHODS: Serum levels of sIL-2R and IL-6 were measured by rapid one-step sandwich enzyme immunoassay and the serum hs-CRP level was measured by Dade Behring BN ProSpec in 32 KD patients before and after intravenous immunoglobulin (IVIG) therapy. Twenty healthy children were used as the controls. RESULTS: Before IVIG therapy serum levels of sIL-2R (9253.41 +/- 2568.38 pg/mL vs 2161.53 +/- 696.92 pg/mL; P < 0.05), IL-6 (57.19 +/- 45.78 ng/mL vs 7.04 +/- 1.69 ng/mL; P < 0.05) and hs-CRP (117.69 +/- 42.05 mg/L vs 1.15 +/- 0.54 mg/L; P < 0.05) in KD patients were significantly higher than those in healthy controls. After IVIG therapy in KD patients serum IL-6 levels returned to normal and sIL-2R and hs-CRP levels decreased significantly but remained significantly higher than controls (P < 0.05). There was a positive correlation between sIL-2R and hs-CRP levels (r=0.60, P < 0.01). IL-6 levels positively correlated with hs-CRP levels in KD patients before IVIG therapy (r=0.68, P < 0.01). CONCLUSIONS: IL-2R, IL-6 and hs-CRP are activated in the development of KD, and they may be of important value in the early diagnosis of KD.

[Clinical value of serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 for the prediction and early diagnosis of coronary artery lesion in patients with Kawasaki disease].

OBJECTIVE: Kawasaki disease (KD) complicated with coronary artery lesion (CAL) seriously threatens survival quality and life of patients, suggesting that it is very important to early predict the risk of CAL and to early diagnose the disease. Nevertheless, up to now there has been no specific clinical biochemical marker for it because of the poor understanding of the pathological process of KD with CAL. Matrix metalloproteinases (MMPs) and their specific tissue inhibitor of metalloproteinases (TIMPs) play an important role in arterial wall extracellular matrix breakdown and remodeling and are involved in CAL in other diseases. In the present study the practical value of serum MMP-9 and TIMP-1 levels in the prediction and early diagnosis of CAL in KD patients was investigated. METHODS: All subjects were from Chinese population. Serum levels of MMP-9 and TIMP-1 were measured by rapid one-step sandwich enzyme immunoassay in 59 KD patients including 15 with CAL and 44 without CAL by 2 D-echocardiography and coronary angiography, and 20 normal healthy children as controls. Blood samples of patients were obtained before and after intravenous immunoglobulin (IVIG) treatment in acute stage, subacute stage and convalescent stage as well. Serum MMP-9 and TIMP-1 levels and the ratio of MMP-9/TIMP-1 were compared by statistical method in KD patients and controls, as well as in KD with CAL and without CAL. RESULTS: In acute stage serum MMP-9 and TIMP-1 levels and the ratio of MMP-9/TIMP-1 were higher (P < 0.01) in patients with KD than those in healthy children. After IVIG treatment in KD patients serum MMP-9 level and the ratio of MMP-9/TIMP-1 decreased (P < 0.01). Before IVIG treatment serum MMP-9 level and the ratio of MMP-9/TIMP-1 were higher (P < 0.01) in patients with CAL than those in patients without CAL, and in acute stage after IVIG treatment serum MMP-9 level of KD patients with CAL was still higher than that of KD patients without CAL. CONCLUSION: In acute stage of KD serum MMP-9 level and the ratio of MMP-9/TIMP-1 were higher in patients with CAL than those in patients without CAL, suggesting that during acute phase of KD the great increase in serum MMP-9 and the imbalance of the MMP-9/TIMP-1 ratio might be high risk factors of KD coronary artery lesion. Therefore, the measurement of serum MMP-9 and TIMP-1 might be of important clinical value in the prediction and the early diagnosis of KD with coronary artery lesion.