Epitope delimitation: A new method for defining epitopes of human IgG-reactive antigenic peptides based on rabbit-recognized epitope motifs.

The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.

Enhanced Cathode Performance: The Heterostructure Construction of LiCoO2@Co3O4@Li6.4La3Zr1.4Ta0.6O12.

In this study, the heterostructure cathode material LiCoO2@Co3O4@Li6.4La3Zr1.4Ta0.6O12 was prepared by coating Li6.4La3Zr1.4Ta0.6O12 on the surface of LiCoO2 through a one-step solid-phase synthesis. The morphology, structure, electrical state, and elemental contents of both pristine and modified materials were assessed through a range of characterization techniques. Theoretical calculations revealed that the LCO@LLZTO material possessed a reduced diffusion barrier compared to LiCoO2, thereby facilitating the movement of Li ions. Electrochemical tests indicated that the capacity retention rate of the modified cathode composites stood at 70.43% following 300 cycles at a 2C rate. This high rate occurred because the Li6.4La3Zr1.4Ta0.6O12 film on the surface enhanced the migration of Li+, and the spinel phase of Co3O4 had better interfacial stability to alleviate the generation of microcracks by inhibiting the phase change from the layered phase to the rock-salt phase, which considerably improved the electrochemical properties.

Mitochondrial targeted modification and anticancer mechanism of natural product ergosterol peroxide.

Ergosterol peroxide (EP) isolated from the edible medicinal fungus Pleurotus ferulae has a wide range of anti-tumor activity, but poor water solubility and low bioavailability limit further application. In this study, EP was structurally modified using triphenylphosphine (TPP+), which combines mitochondrial targeting, amphiphilicity, and cytotoxicity. A series of TPP+-conjugated ergosterol peroxide derivatives (TEn) with different length linker arms were synthesized. The structure-activity relationship showed that the anticancer activity of TEn gradually decreased with the elongation of the linker arm. The compound TE3 has the optimal and broadest spectrum of antitumor effects. It mainly through targeting mitochondria, inducing ROS production, disrupting mitochondrial function, and activating mitochondria apoptosis pathway to exert anti-cervical cancer activity. Among them, TPP+ only acted as a mitochondrial targeting group, while EP containing peroxide bridge structure served as an active group to induce ROS. In vivo experiments have shown that TE3 has better anti-cervical cancer activity and safety than the first-line anticancer drug cisplatin, and can activate the immune response in mice. Although TE3 exhibits some acute toxicity, it is not significant at therapeutic doses. Therefore, TE3 has the potential for further development as an anti-cervical cancer drug.

Progress in Research of Nanotherapeutics for Overcoming Multidrug Resistance in Cancer.

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.

Noble Metal Nanoparticle-Based Photothermal Therapy: Development and Application in Effective Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.

Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.

Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.

Total Flavonoids in Artemisia absinthium L. and Evaluation of Its Anticancer Activity.

To overcome the shortcomings of traditional extraction methods, such as long extraction time and low efficiency, and considering the low content and high complexity of total flavonoids in Artemisia absinthium L., in this experiment, we adopted ultrasound-assisted enzymatic hydrolysis to improve the yield of total flavonoids, and combined this with molecular docking and network pharmacology to predict its core constituent targets, so as to evaluate its antitumor activity. The content of total flavonoids in Artemisia absinthium L. reached 3.80 ± 0.13%, and the main components included Astragalin, Cynaroside, Ononin, Rutin, Kaempferol-3-O-rutinoside, Diosmetin, Isorhamnetin, and Luteolin. Cynaroside and Astragalin exert their cervical cancer inhibitory functions by regulating several signaling proteins (e.g., EGFR, STAT3, CCND1, IGFIR, ESR1). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the anticancer activity of both compounds was associated with the ErbB signaling pathway and FoxO signaling pathway. MTT results showed that total flavonoids of Artemisia absinthium L. and its active components (Cynaroside and Astragalin) significantly inhibited the growth of HeLa cells in a concentration-dependent manner with IC50 of 396.0 ± 54.2 µg/mL and 449.0 ± 54.8 µg/mL, respectively. Furthermore, its active components can mediate apoptosis by inducing the accumulation of ROS.

Multifunctional Nanoplatform for NIR-II Imaging-Guided Synergistic Oncotherapy.

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.

Preparation, Characterization, Photochromic Properties, and Mechanism of PMoA/ZnO/PVP Composite Film.

A novel photochromic heteropolyacid-based composite film consisting of phosphomolybdic acid (PMoA), ZnO, and polyvinylpyrrolidone (PVP) was fabricated by a sol-gel process. The microstructure and photochromic properties of the PMoA/ZnO/PVP were characterized via Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible spectroscopy (UV-Vis). The FTIR spectra showed that the basic structures of ZnO and PVP, and the Keggin structure of PMoA in the PMoA/ZnO/PVP composite film, had not been destroyed during the preparation. The TEM images demonstrated that ZnO presented a rod-like structure, while PMoA was spherical, and many PMoA balls adhered to the surface of the ZnO rods. The XPS spectra of Mo 3d indicated that the valency of Mo atoms in the PMoA/ZnO/PVP was changed by visible light exposure. After visible light irradiation, the PMoA/ZnO/PVP varied from slight yellow to blue, while undergoing an opposite color change upon heating. The discoloration mechanism of the PMoA/ZnO/PVP was consistent with the photoelectron transfer mechanism.

Clinical significance of the CD98hc-CD147 complex in ovarian cancer: a bioinformatics analysis.

Ovarian cancer is one of the most common malignant tumours affecting the female reproductive organs. CD147 (BSG) and CD98hc (SLC3A2) are oncogenes that form the CD98hc-CD147 complex, which regulates the proliferation, metastasis, metabolism, and cell cycle of cancer cells. The roles of the CD98hc-CD147 complex in ovarian cancer remain unclear. We analysed the expression and prognostic value of CD147 and CD98hc in ovarian cancer using the TCGA and ICGC databases. The effect of CD147 and CD98hc on the tumour immune response was analysed using the TIMER database. CD98hc was more highly expressed in normal tissues than primary tumour tissues, while CD147 was more highly expressed in primary tumour tissues than normal tissues. CD98hc expression was significantly associated with neutrophil and dendritic cell levels. CD147 and CD98hc were correlated with DNA repair, the cell cycle, and DNA replication. The CD98hc-CD147 complex could serve as a target for ovarian cancer treatment.

What is already known on this subject? CD98hc and CD147 are oncogenes that induce the proliferation and metastasis of cancer cells. The CD98hc-CD147 complex has been identified as a risk factor for cancer patients and causes resistance to cancer treatment.What do the results of this study add? We confirmed the expression levels of CD98hc and CD147 in ovarian cancer tissues and the effects of these oncogenes on the tumour immune response.What are the implications of these findings for clinical practice and/or further research? The CD98hc-CD147 complex may serve as a new target for ovarian cancer therapy.

In Vitro and In Vivo Dendritic Cell Immune Stimulation Effect of Low Molecular Weight Fucoidan from New Zealand Undaria pinnatifida.

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs' maturation and migration, as well as CD4+ and CD8+ T cells' proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF-κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.

Cecropin-Loaded Zeolitic Imidazolate Framework Nanoparticles with High Biocompatibility and Cervical Cancer Cell Toxicity.

Cecropins (CECs) are insect venom-derived amphiphilic peptides with numerous pharmacological effects, including anti-inflammatory, antibacterial, antiviral, and anti-tumor activities. Cecropins induce tumor cell death by disrupting phospholipid membrane integrity. However, non-specific cytotoxicity and in vivo rapid degradation limit clinical application. Nanotechnologies provide novel strategies for tumor eradication, including nanocarriers that can precisely target drugs to tumor tissue. We report the fabrication of CEC-encapsulated zeolitic imidazolate framework 8 (ZIF-8) nanoparticles (CEC@ZIF-8 NPs) via the preparation of CEC@ZIF-8 NPs in pure water by one-pot stirring. This method yielded morphologically uniform NPs with 20 wt% drug loading capacity and 9% loading efficiency. The NP formulation protected CECs from proteasome degradation, enhanced peptide bioavailability, promoted HeLa tumor cell uptake, and increased antitumor efficacy compared to free CECs. In conclusion, this ZIF-8 encapsulation strategy may enhance the clinical applicability of CECs and other antitumor peptides.

[Hepatic Insulin Resistance and Type 2 Diabetes Mellitus].

Insulin resistance (IR) is a pathological reaction of hyperinsulinemia and impaired glucose tolerance caused by decreased sensitivity of target tissues such as liver to insulin.The pathogenesis of IR as a typical pathological feature of type 2 diabetes is the focus of anti-diabetes research.In this paper,we reviewed the molecular mechanisms of glucose and lipid metabolism,oxidative stress,mitochondrial dysfunction,endoplasmic reticulum stress,inflammation,and hepatic IR in the case of type 2 diabetes mellitus,which might provide new ideas and theoretical guidance for the treatment of diabetes mellitus.

Ultralong and Color-Tunable Room-Temperature Phosphorescence Based on Commercial Melamine for Anticounterfeiting and Information Recognition.

Advances have been made in the research on color-tunable organic ultralong room-temperature phosphorescence (OURTP) materials. Due to the high cost of raw materials, complex and strict synthesis conditions, and low yields, it is hard to obtain cheap commercial OURTP materials within a short time. Therefore, it is of practical significance to research and develop new OURTP functions based on commercialized organic materials. In this study, the OURTP characteristics of melamine (MEL), a kind of commercially available, cheap, and pure organic material, were investigated and explored. MEL was found with color-tunable and excellent OURTP, the average lifetime can reach 0.74 s, and the phosphorescence quantum yield can reach 17%. Since the ratio of molecular phosphorescence of MEL to the ultralong phosphorescence mediated by H-aggregation differs with the excitation wavelength and their luminescence life spans are also different, the color of OURTP materials is dependent on both excitation wavelength and time. Moreover, the OURTP characteristics of MEL can be utilized in anticounterfeiting and information identification.

Recent Progress on the Synthesis of Chiral Sulfones.

Chiral sulfones extensively exist in drugs, agricultural chemicals, chiral organic intermediates, and functional materials. Their importance causes the rapid development of their synthetic methods in recent years. Many transition metal complex catalysts with chiral ligands and chiral organocatalysts are adopted in synthesis of chiral sulfones. Most of the methods to construct chiral sulfones are based on the reduction of unsaturated sulfones and the introduction of sulfone groups into unsaturated hydrocarbons. This review describes all classes of asymmetric reactions for synthesis of chiral sulfones.

[Research progress and analysis on mechanism of polysaccharides against type 2 diabetes mellitus].

Polysaccharides are macromolecular compounds formed by more than 10 monosaccharide molecules linked by glycosidic bonds. Polysaccharides have a wide range of sources, high safety and low toxicity, with a variety of biological activities, such as anti-tumor, anti-virus, immune regulation, lowering blood glucose, and lowering blood lipids. Type 2 diabetes mellitus(T2 DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance and low inflammation. In recent years, the treatment of T2 DM with polysaccharide has become a research hotspot. Polysaccharides can not only make up for the side effects such as hypoglycemia, weight gain, gastrointestinal injury caused by long-term treatment of acarbose, biguanidine and sulfonylurea, but also play an effective role in reducing glucose by regulating glucose metabolism, oxidative stress, inflammatory response, intestinal flora, etc. In this paper, the research progress of polysaccharides in the treatment of T2 DM was reviewed. In addition, the hot spots such as the hypoglycemic activity of polysaccharides with structural modifications were summarized, providing theoretical guidance for the development of active polysaccharide hypoglycemic medicines and the further study of action mechanism.

The Extracts of Artemisia absinthium L. Suppress the Growth of Hepatocellular Carcinoma Cells through Induction of Apoptosis via Endoplasmic Reticulum Stress and Mitochondrial-Dependent Pathway.

Artemisia absinthium L. has pharmaceutical and medicinal effects such as antimicrobial, antiparasitic, hepatoprotective, and antioxidant activities. Here, we prepared A. absinthium ethanol extract (AAEE) and its subfractions including petroleum ether (AAEE-Pe) and ethyl acetate (AAEE-Ea) and investigated their antitumor effect on human hepatoma BEL-7404 cells and mouse hepatoma H22 cells. The cell viability of hepatoma cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis, cell cycle, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) were analyzed by flow cytometry. The levels of proteins in the cell cycle and apoptotic pathways were detected by Western blot. AAEE, AAEE-Pe, and AAEE-Ea exhibited potent cytotoxicity for both BEL-7404 cells and H22 cells through the induction of cell apoptosis and cell cycle arrest. Moreover, AAEE, AAEE-Pe, and AAEE-Ea significantly reduced Δψm, increased the release of cytochrome c, and promoted the cleavage of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) in BEL-7404 and H22 cells. AAEE, AAEE-Pe, and AAEE-Ea significantly upregulated the levels of ROS and C/EBP-homologous protein (CHOP). Further, AAEE, AAEE-Pe, and AAEE-Ea significantly inhibited tumor growth in the H22 tumor mouse model and improved the survival of tumor mice without side effects. These results suggest that AAEE, AAEE-Pe, and AAEE-Ea inhibited the growth of hepatoma cells through induction of apoptosis, which might be mediated by the endoplasmic reticulum stress and mitochondrial-dependent pathway.

A mixed treatment comparison on efficacy and safety of treatments for spasticity caused by multiple sclerosis: a systematic review and network meta-analysis.

OBJECTIVES: This study is aimed at providing a quantitative evaluation on different therapies of spasticity caused by multiple sclerosis. DATA SOURCES: PubMed and Embase database. REVIEW METHODS: We searched for randomized controlled trials that met the requirements. Percentages of improved patients' spasticity scale, mild adverse effect and severe adverse effect were extracted as outcomes. The forest plots accompanied with surface under the cumulative ranking curves were used to reveal the efficacy and safety of these therapies. RESULTS: In all, 23 randomized controlled trials with a total of 2720 patients were included in our study. Cannabinoids and botulinum toxin had shown a significantly better efficacy than placebo in the percentage of improved patients. Botulinum toxin also showed such significant difference compared with tizanidine and baclofen. No significant difference was found in spasticity scale. Cannabinoids, tizanidine and diazepam had significantly more mild adverse effect reports than placebo. Surface under the cumulative ranking curves suggested that cannabinoids, botulinum toxin and transcutaneous electric nerve stimulation were preferable therapies. CONCLUSIONS: We recommended botulinum toxin as the optimal intervention for multiple sclerosis-related spasticity. Cannabinoids and transcutaneous electric nerve stimulation could also be considered as multiple sclerosis-related spasticity treatments but their safety remained to be verified.

Fucoidan Extracted from the New Zealand Undaria pinnatifida-Physicochemical Comparison against Five Other Fucoidans: Unique Low Molecular Weight Fraction Bioactivity in Breast Cancer Cell Lines.

Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines-MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment.