Anhui University of Traditional Chinese Medicine

Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.

coordinative bonds are highly porous, crystalline materials. Their tunable porosity, chemical composition, size and shape, and easy surface functionalization make this large family more and more popular for drug delivery. There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. This article presents an overall review and perspectives of MOFs-based drug delivery systems (DDSs), starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands. Then, the synthesis and characterization of MOFs for DDSs are developed, followed by the drug loading strategies, applications, biopharmaceutics and quality control. Importantly, a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics, diseases therapy and advanced DDSs. In particular, the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed. Finally, challenges in MOFs development for DDSs are discussed, such as biostability, biosafety, biopharmaceutics and nomenclature.

Solid catalysts usually consist of multicomponents, within which interfacial interactions have been recognized as a key factor affecting structures and catalytic performance. Metal–support interactions (MSI) have been extensively studied in oxide-supported metal catalysts (metal/oxide catalysts), in which the important concepts of strong metal–support interactions (SMSI) and electronic metal–support interactions (EMSI) have been well established and their effects on the metal catalysis have been extensively demonstrated. Recently, metal-supported oxide inverse catalysts (oxide/metal inverse catalysts) have emerged as a new type of efficient catalysts, in which the oxide–metal interactions (OMI) strongly influence the oxide catalysis. Herein we comprehensively review the progresses on the MSI of metal/oxide catalysts and OMI of oxide/metal inverse catalysts with aims to emphasize structure sensitivity of MSI and OMI and to introduce the concepts of electronic oxide–metal interactions (EOMI) and electronic oxide–metal strong interactions (EOMSI) in oxide/metal inverse catalysts, in analogy to the concepts of EMSI and SMSI in metal/oxide catalysts. First, we briefly introduce the background of the topic and the interfacial interactions between metals and oxides with emphasis on the nature of metal–support interfacial interactions depending on the electronic structures. Second, the MSI, with an emphasis on the EMSI and SMSI, in metal/oxide catalysts is reviewed with an emphasis on the recently exported size and facet effects on the electronic structures and MSI. Third, the OMI in oxide/metal inverse catalysts is reviewed with an emphasis on introducing the EOMI and EOMSI. Finally, a summary and outlook is given with emphasis on the local nature and structure sensitivity of MSI and OMI.

Objective: Exosomes (Exos) are membrane-encased vesicles derived by nearly all cell types for intercellular communication and regulation. They also received attention for their use as natural therapeutic platforms and drug delivery system. Classically activated M1 macrophages suppress tumor growth by releasing pro-inflammatory factors. This study investigated the suitability of M1-exosomes (M1-Exos) as drug carrier and their effect on the NF-B signal pathway and further detected whether macrophages repolarization can potentiate the antitumor activities of chemotherapeutics. Methods: M1-Exos were isolated from M1-macrophages by ultracentrifugation and characterized by transmission electron, nanoparticle tracking analysis, dynamic light scattering and western blot. Then M1-Exos were used as Paclitaxel (PTX) carriers to prepare a nano-formulation (PTX-M1-Exos). A relatively simple slight sonication method was used to prepare the drug delivery system (PTX-M1-Exos). The cytotoxicity of PTX-M1-Exos on cancer cells was detected by MTT and flow cytometry in vitro. 4T1 tumor bearing mice were used to perform the therapeutic effect of PTX-M1-Exos in vivo.

Lung cancer accounts for a relatively high proportion of malignant tumors. As the most prevalent type of lung cancer, non-small cell lung cancer (NSCLC) is characterized by high morbidity and mortality. Presently, the arsenal of treatment strategies encompasses surgical resection, chemotherapy, targeted therapy and radiotherapy. However, despite these options, the prognosis remains distressingly poor with a low 5-year survival rate. Therefore, it is urgent to pursue a paradigm shift in treatment methodologies. In recent years, the advent of sophisticated biotechnologies and interdisciplinary integration has provided innovative approaches for the treatment of lung cancer. This article reviews the cutting-edge developments in the nano drug delivery system, molecular targeted treatment system, photothermal treatment strategy, and immunotherapy for lung cancer. Overall, by systematically summarizing and critically analyzing the latest progress and current challenges in these treatment strategies of lung cancer, we aim to provide a theoretical basis for the development of novel drugs for lung cancer treatment, and thus improve the therapeutic outcomes for lung cancer patients.

OBJECTIVES: Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti-fibrotic effect of sorafenib. MATERIALS AND METHODS: . In vitro, Fer-1 and DFO were used to block ferroptosis and then explored the anti-fibrotic effect of sorafenib by detecting α-SMA, COL1α1 and fibronectin proteins. Finally, HIF-1α siRNA, plasmid and stabilizers were applied to assess related signalling pathway. RESULTS: -induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins. In sorafenib-treated HSC-T6 cells, ferroptotic events (depletion of SLC7A11, GPX4 and GSH; accumulation iron, ROS and MDA) were discovered. Intriguingly, these ferroptotic events were not appeared in hepatocytes or macrophages. Sorafenib-elicited HSC ferroptosis and ECM reduction were abrogated by Fer-1 and DFO. Additionally, both HIF-1α and SLC7A11 proteins were reduced in sorafenib-treated HSC-T6 cells. SLC7A11 was positively regulated by HIF-1α, inactivation of HIF-1α/SLC7A11 pathway was required for sorafenib-induced HSC ferroptosis, and elevation of HIF-1α could inhibit ferroptosis, ultimately limited the anti-fibrotic effect. CONCLUSIONS: Sorafenib triggers HSC ferroptosis via HIF-1α/SLC7A11 signalling, which in turn attenuates liver injury and fibrosis.

Abstract The increasingly intimate bond connecting soft actuation devices and emerging biomedical applications is triggering the development of novel materials with superb biocompatibility and a sensitive actuation capability that can reliably function as bio-use-oriented actuators in a human-friendly manner. Stimulus-responsive hydrogels are biocompatible with human tissues/organs, have sufficient water content, are similar to extracellular matrices in structure and chemophysical properties, and are responsive to external environmental stimuli, and these materials have recently attracted massive research interest for fabricating bioactuators. The great potential of employing such hydrogels that respond to various stimuli (e.g., pH, temperature, light, electricity, and magnetic fields) for actuation purposes has been revealed by their performances in real-time biosensing systems, targeted drug delivery, artificial muscle reconstruction, and cell microenvironment engineering. In this review, the material selection of hydrogels with multiple stimulus-responsive mechanisms for actuator fabrication is first introduced, followed by a detailed introduction to and discussion of the most recent progress in emerging biomedical applications of hydrogel-based bioactuators. Final conclusions, existing challenges, and upcoming development prospects are noted in light of the status quo of bioactuators based on stimulus-responsive hydrogels.

Dye and nitro-compound pollution has become a significant issue worldwide. The adsorption and degradation of dyes and nitro-compounds have recently become important areas of study. Different methods, such as precipitation, flocculation, ultra-filtration, ion exchange, coagulation, and electro-catalytic degradation have been adopted for the adsorption and degradation of these organic pollutants. Apart from these methods, adsorption, photocatalytic degradation, and chemical degradation are considered the most economical and efficient to control water pollution from dyes and nitro-compounds. In this review, different kinds of dyes and nitro-compounds, and their adverse effects on aquatic organisms and human beings, were summarized in depth. This review article covers the comprehensive analysis of the adsorption of dyes over different materials (porous polymer, carbon-based materials, clay-based materials, layer double hydroxides, metal-organic frameworks, and biosorbents). The mechanism and kinetics of dye adsorption were the central parts of this study. The structures of all the materials mentioned above were discussed, along with their main functional groups responsible for dye adsorption. Removal and degradation methods, such as adsorption, photocatalytic degradation, and chemical degradation of dyes and nitro-compounds were also the main aim of this review article, as well as the materials used for such degradation. The mechanisms of photocatalytic and chemical degradation were also explained comprehensively. Different factors responsible for adsorption, photocatalytic degradation, and chemical degradation were also highlighted. Advantages and disadvantages, as well as economic cost, were also discussed briefly. This review will be beneficial for the reader as it covers all aspects of dye adsorption and the degradation of dyes and nitro-compounds. Future aspects and shortcomings were also part of this review article. There are several review articles on all these topics, but such a comprehensive study has not been performed so far in the literature.

Uniform and water-soluble Ag@reduced graphene oxide (Ag@rGO) nanocomposites can be prepared by a facile approach in the absence of additional reductants, which display much better antibacterial properties than that of pure silver nanoparticles synthesized by microwave irradiation, and an equivalent antibacterial effect in comparison with that of the general antibacterial drug ampicillin. Their skin irritation tests with the use of rat models are taken in order to explore the toxicity of this nanocomposite, which confirm that no oedema or erythema appears on the injured rat skin after exposure to the as-prepared Ag@rGO nanocomposites.

We present the 1.06 Gb sequenced genome of Gastrodia elata, an obligate mycoheterotrophic plant, which contains 18,969 protein-coding genes. Many genes conserved in other plant species have been deleted from the G. elata genome, including most of those for photosynthesis. Additional evidence of the influence of genome plasticity in the adaptation of this mycoheterotrophic lifestyle is evident in the large number of gene families that are expanded in G. elata, including glycoside hydrolases and urease that likely facilitate the digestion of hyphae are expanded, as are genes associated with strigolactone signaling, and ATPases that may contribute to the atypical energy metabolism. We also find that the plastid genome of G. elata is markedly smaller than that of green plant species while its mitochondrial genome is one of the largest observed to date. Our report establishes a foundation for studying adaptation to a mycoheterotrophic lifestyle.

Well-dispersed M@TiO2 (M = Ag, Pd, Au, Pt) nanocomposite particles with a diameter of 200–400 nm can be synthesized on a large scale by a clean photochemical route which does not require any additives using spherical rutile nanoparticles as a support. The sizes of Pt, Au, and Pd nanoparticles formed on the surface of TiO2 particles are about 1 nm, 5 nm, and 5 nm, respectively, and the diameter of Ag nanoparticles is in the range 2–20 nm. Moreover, the noble metal nanoparticles have good dispersity on the particles of the TiO2 support, resulting in excellent catalytic activities. Complete conversion in catalytic CO oxidation is reached at temperatures as low as 333 and 363 K, respectively, for Pt@TiO2 and Pd@TiO2 catalysts. In addition, the antibacterial effects of the as-synthesized TiO2 nanoparticles, silver nanoparticles, and Au@TiO2 and Ag@TiO2 nanocomposites have been tested against Gram-negative Escherichia coli (E. coli) bacteria. The results demonstrate that the presence of the TiO2 matrix enhances the antibacterial effect of silver nanoparticles, and the growth of E. coli can be completely inhibited even if the concentration of Ag in Ag@TiO2 nanocomposite is very low (10 μg/mL).

Drug delivery for tumor theranostics involves the extensive use of the enhanced permeability and retention (EPR) effect. Previously, various types of nanomedicines have been demonstrated to accumulate in solid tumors via the EPR effect. However, EPR is a highly variable phenomenon because of tumor heterogeneity, resulting in low drug delivery efficacy in clinical trials. Because ultrasonication using micro/nanobubbles as contrast agents can disrupt blood vessels and enhance the specific delivery of drugs, it is an effective approach to improve the EPR effect for the passive targeting of tumors. In this review, the basic thermal effect, acoustic streaming, and cavitation mechanisms of ultrasound, which are characteristics that can be utilized to enhance the EPR effect, are briefly introduced. Second, micro/nanobubble-enhanced ultrasound imaging is discussed to understand the validity and variability of the EPR effect. Third, because the tumor microenvironment is complicated owing to elevated interstitial fluid pressure and the deregulated extracellular matrix components, which may be unfavorable for the EPR effect, few new trends in smart bubble drug delivery systems, which may improve the accuracy of EPR-mediated passive drug targeting, are summarized. Finally, the challenging and major concerns that should be considered in the next generation of micro/nanobubble-contrast-enhanced ultrasound theranostics for EPR-mediated passive drug targeting are also discussed.

BACKGROUND: Acupuncture has been used for chronic constipation, but evidence for its effectiveness remains scarce. OBJECTIVE: To determine the efficacy of electroacupuncture (EA) for chronic severe functional constipation (CSFC). DESIGN: Randomized, parallel, sham-controlled trial. (ClinicalTrials.gov: NCT01726504). SETTING: 15 hospitals in China. PARTICIPANTS: Patients with CSFC and no serious underlying pathologic cause for constipation. INTERVENTION: 28 sessions of EA at traditional acupoints or sham EA (SA) at nonacupoints over 8 weeks. MEASUREMENTS: The primary outcome was the change from baseline in mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8. Participants were followed until week 20. RESULTS: 1075 patients (536 and 539 in the EA and SA groups, respectively) were enrolled. The increase from baseline in mean weekly CSBMs during weeks 1 to 8 was 1.76 (95% CI, 1.61 to 1.89) in the EA group and 0.87 (CI, 0.73 to 0.97) in the SA group (between-group difference, 0.90 [CI, 0.74 to 1.10]; P < 0.001). The change from baseline in mean weekly CSBMs during weeks 9 to 20 was 1.96 (CI, 1.78 to 2.11) in the EA group and 0.89 (CI, 0.69 to 0.95) in the SA group (between-group difference, 1.09 [CI, 0.94 to 1.31]; P < 0.001). The proportion of patients having 3 or more mean weekly CSBMs in the EA group was 31.3% and 37.7% over the treatment and follow-up periods, respectively, compared with 12.1% and 14.1% in the SA group (P < 0.001). Acupuncture-related adverse events during treatment were infrequent in both groups, and all were mild or transient. LIMITATIONS: Longer-term follow-up was not assessed. Acupuncturists could not be blinded. CONCLUSION: Eight weeks of EA increases CSBMs and is safe for the treatment of CSFC. Additional study is warranted to evaluate a longer-term treatment and follow-up. PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program.

Abstract Epigenetics including DNA and RNA modifications have always been the hotspot field of life sciences in the post-genome era. Since the first mapping of N6-methyladenosine (m 6 A) and the discovery of its widespread presence in mRNA, there are at least 160-170 RNA modifications have been discovered. These methylations occur in different RNA types, and their distribution is species-specific. 5-methylcytosine (m 5 C) has been found in mRNA, rRNA and tRNA of representative organisms from all kinds of species. As reversible epigenetic modifications, m 5 C modifications of RNA affect the fate of the modified RNA molecules and play important roles in various biological processes including RNA stability control, protein synthesis, and transcriptional regulation. Furthermore, accumulative evidence also implicates the role of RNA m 5 C in tumorigenesis. Here, we review the latest progresses in the biological roles of m 5 C modifications and how it is regulated by corresponding “writers”, “readers” and “erasers” proteins, as well as the potential molecular mechanism in tumorigenesis and cancer immunotherapy.

Activation of hepatic stellate cells (HSCs) represents the primary driving force to promote the progression of chronic cholestatic liver diseases. We previously reported that cholangiocyte‐derived exosomal long noncoding RNA‐H19 (lncRNA‐H19) plays a critical role in promoting cholestatic liver injury. However, it remains unclear whether cholangiocyte‐derived lncRNA‐H19 regulates HSC activation, which is the major focus of this study. Both bile duct ligation (BDL) and Mdr2 knockout (Mdr2 ‐/‐ ) mouse models were used. Wild‐type and H19 maternalΔExon1/+ (H19KO) mice were subjected to BDL. Mdr2 ‐/‐ H19 maternalΔExon1/+ (DKO) mice were generated. Exosomes isolated from cultured mouse and human cholangiocytes or mouse serum were used for in vivo transplantation and in vitro studies. Fluorescence‐labeled exosomes and flow cytometry were used to monitor exosome uptake by hepatic cells. Collagen gel contraction and bromodeoxyuridine assays were used to determine the effect of exosomal‐H19 on HSC activation and proliferation. Mouse and human primary sclerosing cholangitis (PSC)/primary biliary cholangitis (PBC) liver samples were analyzed by real‐time PCR, western blot analysis, histology, and immunohistochemistry. The results demonstrated that hepatic H19 level was closely correlated with the severity of liver fibrosis in both mouse models and human patients with PSC and PBC. H19 deficiency significantly protected mice from liver fibrosis in BDL and Mdr2 ‐/‐ mice. Transplanted cholangiocyte‐derived H19‐enriched exosomes were rapidly and preferentially taken up by HSCs and HSC‐derived fibroblasts, and promoted liver fibrosis in BDL‐H19KO mice and DKO mice. H19‐enriched exosomes enhanced transdifferentiation of cultured mouse primary HSCs and promoted proliferation and matrix formation in HSC‐derived fibroblasts. Conclusion: Cholangiocyte‐derived exosomal H19 plays a critical role in the progression of cholestatic liver fibrosis by promoting HSC differentiation and activation and represents a potential diagnostic biomarker and therapeutic target for cholangiopathies.

The ovarian system comprises vital organs in females and is of great significance for the maintenance of reproductive potential and endocrine stability. Although complex pathogenesis undoubtedly contributes to ovarian aging, increasing attention is being paid to the extensive influence of oxidative stress. However, the role of oxidative stress in ovarian aging is yet to be fully elucidated. Exploring oxidative stress-related processes might be a promising strategy against ovarian aging. In this review, compelling evidence is shown that oxidative stress plays a role in the etiology of ovarian aging and promotes the development of other ovarian aging-related etiologies, including telomere shortening, mitochondrial dysfunction, apoptosis, and inflammation. In addition, some natural antioxidants such as quercetin, resveratrol, and curcumin have a protective role in the ovaries through multiple mechanisms. These findings raise the prospect of oxidative stress modulator-natural antioxidants as therapeutic interventions for delaying ovarian aging.

Trimethylamine N-oxide (TMAO) is a biologically active molecule generated by the gut microbiota. Accumulating evidences have indicated a close association between high plasma TMAO levels and the risk of developing atherosclerosis (AS). AS is considered a chronic inflammatory disease initiated by vascular endothelial inflammatory injury. Both observational and experimental studies suggest that TMAO can cause endothelial inflammatory injury. However, a clear mechanistic link between TMAO and vascular inflammation of AS is not yet summarized. In this review, we discuss the association between TMAO and AS and focus on the potential role of TMAO in endothelial inflammatory injury. Finally, the utility of TMAO-targeted therapeutic strategies for the treatment of AS is also analyzed.

Importance: Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking. Objective: To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis. Data Sources: A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included "(lichen planus or LP) and (prevalence or incidence or epidemiology)." No language restriction was applied. Study Selection: Observational descriptive studies investigating the prevalence and incidence of OLP were included. Data Extraction and Synthesis: Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence. Main Outcomes and Measures: The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic. Results: Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462 993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191 963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older. Conclusions and Relevance: This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.

In recent years,many domestic and overseas scholars pay close attention to prostate-specific membrane antigen which is a specific prostate cancermarker. This article review focuses on the structure and properties of prostate-specific membrane antigen as well as the role of PSMA in the treatment of prostate cancer.

A membrane protein is a protein molecule that is attached to,or integrated into the membrane of a cell or an organelle.As the membrane protein is a good target for drugs,more than 80% of the drugs on the present market take the effect on the membrane protein.Therefore,it is significant to study the membrane proteins.However,the traditional study on membrane proteomics is obstructed by the difficulties in solubilizing,separating,and identifying membrane proteins.This review summarizes the structure of membrane proteins,the significant role of the membrane proteins on the cell physiology and the human diseases,the potential of the membrane proteins to be the target for drugs and the techniques of the research on the membrane proteomics.