Recent Strategies to Develop Conjugated Polymers for Detection and Therapeutics.

The infectious diseases resulting from pathogenic microbes are highly contagious and the source of infection is difficult to control, which seriously endangers life and public health safety. Although the emergence of antibiotics has a good therapeutic effect in the early stage, the massive abuse of antibiotics has brought about the evolution of pathogens with drug resistance, which has gradually weakened the lethality and availability of antibiotics. Cancer is a more serious disease than pathogenic bacteria infection, which also threatens human life and health. Traditional treatment methods have limitations such as easy recurrence, poor prognosis, many side effects, and high toxicity. These two issues have led to the exploration and development of novel therapeutic agents (such as conjugated polymers) and therapeutic strategies (such as phototherapy) to avoid the increase of drug resistance and toxic side effects. As a class of organic polymer biological functional materials with excellent photoelectric properties, Conjugated polymers (CPs) have been extensively investigated in biomedical fields, such as the detection and treatment of pathogens and tumors due to their advantages of easy modification and functionalization, good biocompatibility and low cost. A rare comprehensive overview of CPs-based detection and treatment applications has been reported. This paper reviews the design strategies and research status of CPs used in biomedicine in recent years, introduces and discusses the latest progress of their application in the detection and treatment of pathogenic microorganisms and tumors according to different detection or treatment methods, as well as the limitations and potential challenges in prospective exploration.

Prognostic, Immunological, and Mutational Analysis of MTA2 in Pan-Cancer and Drug Screening for Hepatocellular Carcinoma.

BACKGROUND: Metastasis-associated protein 2 (MTA2) is a member of the metastasis-associated transcriptional regulator family and is a core component of the nucleosome remodeling and histone deacetylation complex. Despite growing evidence that MTA2 plays a crucial role in the tumorigenesis of certain cancers, no systematic pan-cancer analysis of MTA2 is available to date. Therefore, the aim of our study is to explore the prognostic value of MTA2 in 33 cancer types and to investigate its potential immune function. METHODS: by comprehensive use of databases from TCGA, GTEx, GEO, UCSC xena, cBioPortal, comPPI, GeneMANIA, TCIA, MSigDB, and PDB, we applied various bioinformatics approaches to investigate the potential role of MTA2, including analyzing the association of MTA2 with MSI, prognosis, gene mutation, and immune cell infiltration in different tumors. We constructed a nomogram in TCGA-LIHC, performed single-cell sequencing (scRNA-seq) analysis of MTA2 in hepatocellular carcinoma (HCC), and screened drugs for the treatment of HCC. Finally, immunohistochemical experiments were performed to verify the expression and prognostic value of MTA2 in HCC. In vitro experiments were employed to observe the growth inhibition effects of MK-886 on the HCC cell line HepG2. RESULTS: The results suggested that MTA2 was highly expressed in most cancers, and MTA2 expression was associated with the prognosis of different cancers. In addition, MTA2 expression was associated with Tumor Mutation Burden (TMB) in 12 cancer types and MSI in 8 cancer types. Immunoassays indicated that MTA2 positively correlated with activated memory CD4 T cells and M0 macrophage infiltration levels in HCC. ScRNA-seq analysis based on the GEO dataset discovered that MTA2 was significantly expressed in T cells in HCC. Finally, the eXtreme Sum (Xsum) algorithm was used to screen the antitumor drug MK-886, and the molecular docking technique was utilized to reveal the binding capacity between MK-886 and the MTA2 protein. The results demonstrated excellent binding sites between them, which bind to each other through Π-alkyl and alkyl interaction forces. An immunohistochemistry experiment showed that MTA2 protein was highly expressed in HCC, and high MTA2 expression was associated with poor survival in HCC patients. MK-886 significantly inhibited the proliferation and induced cell death of HepG2 cells in a dose-dependent manner. CONCLUSIONS: Our study demonstrated that MTA2 plays crucial roles in tumor progression and tumor immunity, and it could be used as a prognostic marker for various malignancies. MK-886 might be a powerful drug for HCC.

Structural characterization and anti-osteoporosis effects of polysaccharide purified from Eucommia ulmoides Oliver cortex based on its modulation on bone metabolism.

EuOCP3, with a molecular weight of 38.1 kDa, is an acidic polysaccharide purified from Eucommia ulmoides Oliver cortex. Herein, we determined that the main backbone of EuOCP3 was predominantly composed of →4)-α-GalpA-(1 â†’ 4)-α-GalpA-(1→, →4)-α-GalpA-(1 â†’ 5)-α-Araf-(1→, →4)-α-GalpA-(1 â†’ 2)-α-Rhap-(1→, and →4)-α-GalpA-(1 â†’ 5)-α-Araf-(1 â†’ 2)-α-Rhap-(1 â†’ repeating blocks, which were connected by →2,3,5)-α-Araf-(1→. The side chains, substituted at C-2 and C-5 of →2,3,5)-α-Araf-(1→, contained T-ß-Araf→ and T-ß-Araf â†’ 4)-α-GalpA-(1 â†’ residues. In dexamethasone (Dex)-induced osteoporosis (OP) mice, EuOCP3 treatment restored cortical bone thickness, increased mineralized bone area, enhanced the number of osteoblasts, and decreased the number of osteoclasts on the surface of cortical bone. Combining analysis of gut microflora, serum metabolite profiles, and biological detection results, we demonstrated that EuOCP3 regulated the abundance of specific species within the gut microflora, such as g_Dorea and g_Prevotella, and ameliorated oxidative stress. In turn, enhancement of osteogenic function and restoration of bone metabolism via the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway was indicated. The current findings contribute to understanding the potential of EuOCP3 in anti-OP treatment.

A review on natural products with cage-like structure.

Natural products with diverse structures and significant biological activities are essential sources of drug lead compounds, and play an important role in the research and development of innovative drugs. Cage-like compounds have various structures and are widely distributed in nature, especially caged xanthones isolated from Garcinia genus, paeoniflorin and its derivatives isolated from Paeonia lactiflora Pall, tetrodotoxin (TTX) and its derivatives, and so on. In recent years, the development and utilization of cage-like compounds have been a research hotspot in chemistry, biology and other fields due to their special structures and remarkable biological activities. In this review, we mainly summarized the cage-like compounds with various structures found and isolated from natural drugs since 1956, summarized its broad biological activities, and introduced the progress in the biosynthesis of some compounds, so as to provide a reference for the discovery of more novel compounds, and the development and application of innovative drugs.

Six new sesquiterpenoids from the fruits of Xanthium italicum.

Four new germacrane-type sesquiterpenoids (1-4) and two new guaiane-type sesquiterpenoids (5-6) were isolated from the fruits of Xanthium italicum Moretti. The structures of the new compounds were elucidated on the basis of spectroscopic analysis and X-ray diffraction experiment. Compounds 1, 2 and 6 showed the anti-inflammatory effects against the activation of NF-κB induced by lipopolysaccharide (LPS) with IC50 values of 20.12, 22.89 and 68.66 µM, respectively.

Five new Erythrina alkaloids from the stems of Erythrina corallodendron.

Five new Erythrina alkaloids and five known E. alkaloids were isolated from a 95% ethanol extract of the stems of Erythrina corallodendron L. Their chemical structures were elucidated by UV, IR, HRESIMS, NMR and X-ray. Furthermore, the analgesic activities of E. alkaloids 1, 2 and 6 were evaluated by using an acetic acid-induced writhing test in mice, and their writhing inhibition rates were 67.9%, 64.6% and 70.3% at doses of 20 mg/kg, respectively.

New lignans and diterpenoid glycosides from the fruits of Xanthium italicum Moretti.

A pair of new lignans [(+)- 1 and (-)- 1] and three new compounds (2-4), together with a known compound 5, were isolated from the fruits of Xanthium italicum Moretti. The structures of these compounds were determined on the basis of spectroscopic analysis, particularly HR-ESI-MS and 1 D and 2 D NMR. Compounds 2 and 3 showed antinociceptive effects in an acetic acid-induced writhing test in mice with the writhe inhibition rates of 80.50% and 67.89% at the dose of 20 mg/kg, respectively.

[Research advances in methods of cyclezation mechanism of sesquiterpenes].

Terpenes are the largest group of natural products and contain the widest assortment of structural types. Terpene cyclization is also the most complex reaction found in nature. For a long time, terpenoids with diverse structures have attracted natural product chemists to explore their biosynthesis mechanism. Such a large number of terpene skeletons are catalyzed by enzymes called terpene synthase. Sesquiterpene synthase is a kind of terpene synthase, which can catalyze the cyclization of linear precursor farnesyl pyrophosphate(FPP) to sesquiterpene skeletons. Sesquiterpene synthase cyclize a single precursor FPP into many sesquiterpene skeletons. With the continuous discovery of sesquiterpene synthase, the cyclization mechanism of sesquiterpene synthase has been studied deeply. In recent years, with the development and improvement of isotope labeling of substrate FPP and structural analysis of sesquiterpene synthase, the structure and cyclization mechanism of sesquiterpene synthase have been studied more systematically and accurately. In this review, we reviewed the progress of the research methods on the mechanism of sesquiterpene cyclization by substrate isotope labeling and protein structure, as well as the summary and prospect of sesquiterpene synthase research.

[Preliminary study of dihydroartemisin in inhibiting invasion and metastasis of hepatoma cells].

It is reported that dihydroartemisinin could reduce the expression of phosphorylated adhesion kinase and matrix metalloproteinase-2, inhibit the growth, migration and invasion of ovarian cancer cells, promote the formation of Treg cells through TGF-beta/Smad signaling pathway, and play an immunosuppressive role; dihydroartemisinin could also inhibit the growth of lung cancer cells by inhibiting the expression of vascular endothelial growth factor(VEGF) receptor KDR. However, there are few studies on dihydroartemisinin in hepatocellular carcinoma cells. In order to preliminarily explore the effect of dihydroartemisinin on invasion and metastasis of hepatocellular carcinoma cells, CCK-8 method and crystal violet staining were used to detect the effect of dihydroartemisinin on the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H. The effects of dihydroartemisinin on the invasion and metastasis of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H were studied by using cell wound healing and Transwell. Western blot was used to detect the protein expression of epidermal growth factor receptor(EGFR) and its downstream signaling pathway in cells treated with dihydroartemisinin for 48 hours. The results showed that dihydroartemisinin could inhibit the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H at 25 µmol·L~(-1). As compared with the control group, the number of cell clones was significantly reduced, and the ability of cell migration and invasion was weakened. Western blot results showed that as compared with the control group, dihydroartemisinin group could down-regulate the protein expression of EGFR and its downstream signaling pathways p-AKT, p-ERK, N-cadherin, Snail and Slug, and up-regulate the expression of E-cadherin protein, thus affecting the migration, invasion and metastasis of hepatocellular carcinoma cells 7402 and MHCC97 H.

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast.

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.

Safe utilization and zoning on natural selenium-rich land resources: a case study of the typical area in Enshi County, China.

Selenium (Se) is an essential trace element. However, Se in soil is often accompanied by heavy metals, such as cadmium (Cd), because of geological background. The safe utilization of such Se-rich land resources remains a challenge. A typical Se-rich area located in Enshi County, China, was systematically investigated with geochemical and epidemiological methods. The results show that Se in the topsoil is 0.84 ± 1.39 µg/g, whereas that of Cd is 0.93 ± 1.63 µg/g. And the concentration of Se and Cd in corn is 0.22 ± 0.96 µg/g and 0.15 ± 0.32 µg/g, respectively, which is mainly related to the high concentrations in soil. The benchmark dose limit of urinary Cd for ß2-microglobulin in subjects (n = 160) was calculated as 3.27 µg/g Cr. In view of crop-human dose effect and combining the relationship among the concentrations of crops and human biomarkers and the concentrations of crops and topsoil, this study established the models of land resource safety zoning. With that, the risk screening value of Cd in the soil could be obtained as 0.98 µg/g in this typical area. The proportions of priority utilization, safe utilization, and strict management of agricultural land area were 58.85%, 22.90%, and 18.25%, respectively, in Enshi, China. These results could provide scientific support for local agricultural development and ecological sustainability.

[Land Safety Zoning Method in High-Selenium and High-Cadmium Areas].

The selenium in the soil of Enshi, Hubei Province, is very rich, but there is also a certain degree of cadmium pollution risk. To scientifically utilize selenium-rich resources, a typical high-selenium and high-cadmium area in Shashi Township, Enshi City was selected as the research object. Combined with the corn cadmium selenium absorption model, a land safety zoning method was proposed. Comparing the health effects of selenium with the results of land safety zoning, it was found that the antagonism of selenium on cadmium can reduce the area of strict control of agricultural areas, and improve land use efficiency. Combined with the characteristics of cadmium and selenium in various crops in the study area, it is recommended for priority protection areas and safe-use areas to vigorously develop selenium-enriched agricultural products, and grow corn and tea in the structural adjustment area.

Hemorheological study and treatment with enema retention of Li Chong Tang combined with moxibustion in women suffering from chronic pelvic inflammatory diseases.

The study was undertaken to investigate the blood stasis of chronic pelvic inflammatory disease (PID) with scientific method, hemorheology. The whole blood viscosities of chronic PID increased significantly compared with normal level, which was consistent with the blood stasis of Traditional Chinese Medicine (TCM) theory. Moreover, sixty women suffering from chronic PID were treated with Enema Retention of Li Chong Tang Combined with Moxibustion (ERM) for 6 weeks. The chronic PID score and the whole blood viscosity were evaluated before and after the ERM. The parameters of whole blood viscosities at low, median and high shear rate of chronic PID group decreased from 12.32±0.31, 6.66±0.13 and 5.15±0.52, to the normal levels, 9.19±0.13, 5.42±0.56 and 4.34±0.43 (p<0.05) after therapy of ERM and the symptoms score decreased from 13.73±3.7 to 3.8±1.4 (p<0.05), which shows that the ERM is an effective therapy method to treat chronic PID.