Is Ancient Medical Treatment an Option for Curating Osteosarcoma Combined with Chemotherapy? A Basic Analysis of Clinic Pharmacy.

BACKGROUND: As a malignant tumor, osteosarcoma (OS) ranks first place among adolescent cancers and is susceptible to developing resistance to chemotherapeutic agents. Differently, traditional Chinese medicine (TCM) has multiple pharmacodynamic targets and complex biological components, which can inhibit tumor survival and drug resistance and gradually play an important role in the treatment of sarcoma. METHODS: This study is to systematically evaluate the safety and efficacy of TCM combined with chemotherapy performed in the clinical treatment of OS. Based on multiple mainstream databases, eleven articles on the relationship between natural products and chemotherapy involving 656 patients were selected from all the literature published as of June 2022. Revman 5.4 software was used for a comprehensive search analysis, supplemented by established exclusion criteria, the Jadad scale, and the evaluation methods provided by Cochrane. RESULTS: The efficiency of TCM combined with chemotherapy was significantly increased compared with chemical drugs alone [OR=2.56, 95% CI (1.36,4.79), Z=2.92, P=0.003]. Meanwhile, the adverse reactions such as nausea and vomiting, hepatotoxicity, and hematological changes caused by chemical drugs were alleviated correspondingly. CONCLUSION: This study indicates that the mode of TCM combined with chemotherapy sheds light on the clinical treatment of OS, which is much better than the one-way mode.

The Pathological Factors Involved in Current In Vitro Atherosclerotic Models.

Cardiovascular disease stemmed from atherosclerosis (AS) is well recognized to be the predominant cause of global death. To comprehensively clarify the pathogenesis of AS, exploit effective drugs, as well as develop therapeutic solutions, various atherosclerotic models were constructed in vitro and widely utilized by the scientific community. Compared with animal models, the in vitro atherosclerotic models play a prominent role not only in the targeted research of single pathological factor related to AS in the human derived system, but also in the combined study on multipathological factors leading to AS, thereby contributing tremendously to the in-depth elucidation of atherosclerotic pathological process. In the current review, a variety of pathological factors incorporated into the existing atherosclerotic models in vitro are broadly elaborated, including the pathological mechanism, in vitro simulation approaches, and the desired improvement perspectives for reproducing each pathological factor. In addition, this review also summarizes the advantages and disadvantages of current atherosclerotic models as well as their potential functionality. Finally, the promising aspects for future atherosclerotic models in vitro with potential advances are also discussed.

Advances in Alzheimer's Disease-Associated Aß Therapy Based on Peptide.

Alzheimer's disease (AD) urgently needs innovative treatments due to the increasing aging population and lack of effective drugs and therapies. The amyloid fibrosis of AD-associated ß-amyloid (Aß) that could induce a series of cascades, such as oxidative stress and inflammation, is a critical factor in the progression of AD. Recently, peptide-based therapies for AD are expected to be great potential strategies for the high specificity to the targets, low toxicity, fast blood clearance, rapid cell and tissue permeability, and superior biochemical characteristics. Specifically, various chiral amino acids or peptide-modified interfaces draw much attention as effective manners to inhibit Aß fibrillation. On the other hand, peptide-based inhibitors could be obtained through affinity screening such as phage display or by rational design based on the core sequence of Aß fibrosis or by computer aided drug design based on the structure of Aß. These peptide-based therapies can inhibit Aß fibrillation and reduce cytotoxicity induced by Aß aggregation and some have been shown to relieve cognition in AD model mice and reduce Aß plaques in mice brains. This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of Aß. We further describe some analysis methods for evaluating the inhibitory effect and point out the challenges in these areas, and possible directions for the design of AD drugs based on peptides, which lay the foundation for the development of new effective drugs in the future.

Visualization of Cell Membrane Tension Regulated by the Microfilaments as a "Shock Absorber" in Micropatterned Cells.

The extracellular stress signal transmits along the cell membrane-cytoskeleton-focal adhesions (FAs) complex, regulating the cell function through membrane tension. However, the mechanism of the complex regulating membrane tension is still unclear. This study designed polydimethylsiloxane stamps with specific shapes to change the actin filaments' arrangement and FAs' distribution artificially in live cells, visualized the membrane tension in real time, and introduced the concept of information entropy to describe the order degree of the actin filaments and plasma membrane tension. The results showed that the actin filaments' arrangement and FAs' distribution in the patterned cells were changed significantly. The hypertonic solution resulted in the plasma membrane tension of the pattern cell changing more evenly and slowly in the zone rich in cytoskeletal filaments than in the zone lacking filaments. In addition, the membrane tension changed less in the adhesive area than in the non-adhesive area when destroying the cytoskeletal microfilaments. This suggested that patterned cells accumulated more actin filaments in the zone where FAs were difficult to generate to maintain the stability of the overall membrane tension. The actin filaments act as shock absorbers to cushion the alternation in membrane tension without changing the final value of membrane tension.

Accurate detection of reactive oxygen species by tuning an elastic motif (GPGGA)4 in nanopores.

We have developed a reactive oxygen species (ROS) sensor based on nanopores modified with GGGCEG(GPGGA)4CEG. The formation of an intramolecular disulfide bond oxidized by ROS leads to conformation changes in GGGCEG(GPGGA)4CEG, which then induces an obvious change in the size of the nanopores and a corresponding ionic current change. This work allows the accurate and dynamic monitoring of ROS through the combination of (GPGGA)4 and nanopores.

The Road to Unconventional Detections: Paper-Based Microfluidic Chips.

Conventional detectors are mostly made up of complicated structures that are hard to use. A paper-based microfluidic chip, however, combines the advantages of being small, efficient, easy to process, and environmentally friendly. The paper-based microfluidic chips for biomedical applications focus on efficiency, accuracy, integration, and innovation. Therefore, continuous progress is observed in the transition from single-channel detection to multi-channel detection and in the shift from qualitative detection to quantitative detection. These developments improved the efficiency and accuracy of single-cell substance detection. Paper-based microfluidic chips can provide insight into a variety of fields, including biomedicine and other related fields. This review looks at how paper-based microfluidic chips are prepared, analyzed, and used to help with both biomedical development and functional integration, ideally at the same time.

The role of Actopaxin in tumor metastasis.

Actopaxin is a newly discovered focal adhesions (FAs) protein, actin-binding protein and pseudopodia-enriched molecule. It can not only bind to a variety of FAs proteins (such as Paxillin, ILK and PINCH) and non-FAs proteins (such as TESK1, CdGAP, ß2-adaptin, G3BP2, ADAR1 and CD29), but also participates in multiple signaling pathways. Thus, it plays a crucial role in regulating important processes of tumor metastasis, including matrix degradation, migration, and invasion, etc. This review covers the latest progress in the structure and function of Actopaxin, its interaction with other proteins as well as its involvement in regulating tumor development and metastasis. Additionally, the current limitations for Actopaxin related studies and the possible research directions on it in the future are also discussed. It is hoped that this review can assist relevant researchers to obtain a deep understanding of the role that Actopaxin plays in tumor progression, and also enlighten further research and development of therapeutic approaches for the treatment of tumor metastasis.

The explorations of dynamic interactions of paxillin at the focal adhesions.

Paxillin is one of the most important adapters in integrin-mediated adhesions that performs numerous crucial functions relying on its dynamic interactions. Its structural behavior serves different purposes, providing a base for several activities. The various domains of paxillin display different functions in the whole process of cell movements and have a significant role in cell adhesion, migration, signal transmission, and protein-protein interactions. On the other hand, some paxillin-associated proteins provide a unique spatiotemporal mechanism for regulating its dynamic characteristics in the tissue homeostasis and make it a more complex and decisive protein at the focal adhesions. This review briefly describes the structural adaptations and molecular mechanisms of recruitment of paxillin into adhesions, explains paxillin's binding dynamics and impact on adhesion stability and turnover, and reveals a variety of paxillin-associated regulatory mechanisms and how paxillin is embedded into the signaling networks.

The raft cytoskeleton binding protein complexes personate functional regulators in cell behaviors.

Several cytoskeleton proteins interact with raft proteins to form raft-cytoskeleton binding protein complexes (RCPCs) that control cell migration and adhesion. The purpose of this paper is to review the latest research on the modes and mechanisms by which a RCPC controls different cellular functions. This paper discusses RCPC composition and its role in cytoskeleton reorganization, as well as the latest developments in molecular mechanisms that regulate cell adhesion and migration under normal conditions. In addition, the role of some external stimuli (such as stress and chemical signals) in this process is further debated, and meanwhile potential mechanisms for RCPC to regulate lipid raft fluidity is proposed. Thus, this review mainly contributes to the understanding of RCPC signal transduction in cells. Additionally, the targeted signal transduction of RCPC and its mechanism connection with cell behaviors will provide a logical basis for the development of unified interventions to combat metastasis related dysfunction and diseases.

A systematic review on active sites and functions of PIM-1 protein.

The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation, differentiation, migration, and other life activities. Many studies have related these functions to its molecular structure, subcellular localization and expression level. However, recognition of specific active sites and their effects on the activity of this constitutively active kinase is still a challenge. Based on the close relationship between its molecular structure and functional activity, this review covers the specific residues involved in the binding of ATP and different substrates in its catalytic domain. This review then elaborates on the relevant changes in protein conformation and cell functions after PIM-1 binds to different substrates. Therefore, this intensive study can improve the understanding of PIM-1-regulated signaling pathways by facilitating the discovery of its potential phosphorylation substrates.

Impact of RIM-BPs in neuronal vesicles release.

Accurate signal transmission between neurons is accomplished by vesicle release with high spatiotemporal resolution in the central nervous system. The vesicle release occurs mainly in the active zone (AZ), a unique area on the presynaptic membrane. Many structural proteins expressed in the AZ connect with other proteins nearby. They can also regulate the precise release of vesicles through protein-protein interactions. RIM-binding proteins (RIM-BPs) are one of the essential proteins in the AZ. This review summarizes the structures and functions of three subtypes of RIM-BPs, including the interaction between RIM-BPs and other proteins such as Bassoon and voltage-gated calcium channel, their significance in stabilizing the AZ structure in the presynaptic region and collecting ion channels, and ultimately regulating the fusion and release of neuronal vesicles.

Total flavonoids of Selaginella pulvinata alleviates cognitive impairment in mice.

Cognitive impairment (CI) refers to dysfunctional cognition, which encompasses a spectrum of disorders, ranging from mild cognitive impairment to dementia. Any factor that results in cortical damage may cause CI. Total flavonoids of Selaginella pulvinata (TFSP), have shown promising antioxidant and protective effects in animal models. In the present study, mice were intraperitoneally treated with scopolamine, sodium nitrite or 45% ethanol to induce memory impairment, and the effects were assessed using a step-down test. After performing the behavioural test, hippocampal sections were collected for anatomical analysis, and the brain and serum levels of memory-related molecules were evaluated. The results showed that TFSP improved memory in a mouse model of CI significantly. Serum data were consistent with the behavioural results: TFSP increased blood acetylcholine levels through modulation of the acetylcholinesterase and choline acetyltransferase levels. It also ameliorated oxidative stress in neurons, increasing superoxide dismutase, glutathione peroxidase and inhibiting nitric oxide synthase levels in the brain. These results suggest that TFSP may exhibit potential as a clinical treatment for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and senile dementia.

Bladder cancer hunting: A microfluidic paper-based analytical device.

Bladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high-precision instrument, well-trained operators, and high cost. In this study, a microfluidic paper-based analytical device (µPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well-beings as experiment and control groups, respectively, to verify the working efficiency of µPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home-based self-detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.

S100A4: a novel partner for heat shock protein 47 in antler stem cells and insight into the calcium ion-induced conformational changes.

S100A4 is a multiple-function protein highly expressed in tumor or stem cells. We found S100A4 was a novel protein partner for heat shock protein 47 (HSP47) in deer antlerogenic periosteum cells (AP cells), indicating that S100A4 could bind with HSP47. S100A4 had both calcium-dependent and calcium-independent patterns (labeled as SCd and SCi, respectively) to execute different biological activities. Homology models of HSP47, SCd and SCi were constructed. HSP47:collagen model, HSP47:collagen I-V, HSP47:SCd and HSP47:SCi complexes were built using ZDOCK software. Together with free SCd and SCi, 200 ns molecular dynamic (MD) simulations were performed to analyze binding free energies and SCi/SCd conformational changes. The energetic results showed that SCi had the strongest affinity to HSP47, and followed by collagens. SCd had little interaction with HSP47. Decomposition energy results showed that collagen model interacted with HSP47 mainly though neutral amino acids. When SCi bound with HSP47, the majority of mediated amino acids were charged. These results indicated that SCi could compete with collagen on the binding site of HSP47. Root mean square fluctuation (RMSF) values and cross-correlation matrices of principal component analysis (PCA) were calculated to evaluate the SCi/SCd structural variation during MD simulation. Both HSP47 and Ca2+ could stabilize the conformation of SCi/SCd. The loops interacting with Ca2+s and linking the two EF-hand motifs were impacted particularly. The relative moving directions of α-helices in EF-hands were distinct by the binding effect of HSP47 and Ca2+. We found that SCi may regulate the differentiation of AP cells by disturbing the interaction between HSP47 and collagen. Communicated by Ramaswamy H. Sarma.

Antheraea pernyi (Lepidoptera: Saturniidae) and Its Importance in Sericulture, Food Consumption, and Traditional Chinese Medicine.

Sericulture was developed in China in ancient times. Antheraea pernyi Guérin-Méneville was domesticated at least 2,000 yr ago, and Chinese farmers developed artificial rearing of A. pernyi before the 17th century. Today, >60,000 tons of cocoons are produced in China each year, which accounts for 90% of the world production. Despite the widespread utilization of A. pernyi in China and a long history of domestic research, the knowledge of A. pernyi outside China is limited. Therefore, we have in this paper summarized the production, usage, and breeding of A. pernyi. The foremost usage of A. pernyi is as silk producers; however, about 55-70% is used for other purposes. In this paper, we give examples of how the different developmental stages are used as a food source for human consumption and in traditional Chinese medicine, both directly in different preparations and also as a nutrient source for rearing medicinal fungi.

Isolation and characterization of a spotted leaf 32 mutant with early leaf senescence and enhanced defense response in rice.

Leaf senescence is a complex biological process and defense responses play vital role for rice development, their molecular mechanisms, however, remain elusive in rice. We herein reported a rice mutant spotted leaf 32 (spl32) derived from a rice cultivar 9311 by radiation. The spl32 plants displayed early leaf senescence, identified by disintegration of chloroplasts as cellular evidence, dramatically decreased contents of chlorophyll, up-regulation of superoxide dismutase enzyme activity and malondialdehyde, as physiological characteristic, and both up-regulation of senescence-induced STAY GREEN gene and senescence-associated transcription factors, and down-regulation of photosynthesis-associated genes, as molecular indicators. Positional cloning revealed that SPL32 encodes a ferredoxin-dependent glutamate synthase (Fd-GOGAT). Compared to wild type, enzyme activity of GOGAT was significantly decreased, and free amino acid contents, particularly for glutamate and glutamine, were altered in spl32 leaves. Moreover, the mutant was subjected to uncontrolled oxidative stress due to over-produced reactive oxygen species and damaged scavenging pathways, in accordance with decreased photorespiration rate. Besides, the mutant showed higher resistance to Xanthomonas oryzae pv. Oryzae than its wild type, coupled with up-regulation of four pathogenesis-related marker genes. Taken together, our results highlight Fd-GOGAT is associated with the regulation of leaf senescence and defense responses in rice.

Comparative proteomics analysis of human osteosarcoma by 2D DIGE with MALDI-TOF/TOF MS.

Osteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. However, controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel protein targets will be critical to identify the path toward improving outcomes for patients. We attempted to identify potential protein markers or therapy targets of osteosarcoma and give a glance at tumorigenesis of osteosarcoma. A sensitive and accurate method was employed in comparative proteomic analysis between benign tumor and osteosarcoma. Tumor tissues obtained by open biopsy before induction chemotherapy were investigated With 2D DIGE and MALDI-TOF/TOF MS, 22 differentially expressed proteins were identified after database searching, including 8 up-regulated and 14 down-regulated proteins. We also validated the expression levels of interesting proteins(have higher Ratios(tumor/normal)) by Western blotting assay. Annotating by bioinformatic tools, we found structural and signal transduction associated proteins were in large percentage among altered level proteins. In particular, some low abundant proteins involving translation and transcription, such as EEF2(Elongation Factor 2), LUM Lumican 23 kDa Protein) and GTF2A2(Transcription Initiation Factor Iia Gamma Chain.), were firstly reported by our study comparing to previous observations. Our findings suggest that these differential proteins may be potential biomarkers for diagnosis or molecules for understanding of osteosarcoma tumorigenesis, coming with biologic, preclinical, and clinical trial efforts being described to improve outcomes for patients.

The effects of velvet antler polypeptides on the phenotype and related biological indicators of osteoarthritic rabbit chondrocytes.

OBJECTIVE: To study the effects of velvet antler polypeptides (VAPs) on osteoarthritic chondrocytes (OCs) in rabbits. METHODS: An osteoarthritic rabbit model was established according to Hulth's method. OCs were isolated and cultured for observation of the cell cycle. Cell proliferation was detected by MTT assay and the cell cycle was monitored by flow cytometry. The phenotype was determined by toluidine blue staining as well as immunohistochemical staining for collagen type II. The expression of MMP-1, MMP-3, MMP-13, TIMP-1, and collagen I and X mRNA by chondrocytes was assayed by RT-PCR. RESULTS: The VAPs had no obvious proliferative effect on OCs and did not affect the cell cycle. However, they significantly reduced the proportion of early apoptotic cells in a dose-dependent manner. Further, VAPs inhibited the expression of collagen I and X mRNA and induced abnormal expression of MMP-1 and MMP-13 mRNA. VAPs had no significant effect on MMP-3 and TIMP-1 mRNA levels. The toluidine blue and collagen type II immunohistochemical staining intensities of VAP-treated chondrocytes were positively correlated with the concentration of VAPs used. CONCLUSION: VAPs had no significant effect on OC proliferation and the cell cycle, but did increase the glycosaminoglycan (GAG) and collagen type II expression levels in the extracellular matrix, and down-regulated collagen I and X mRNA expression. Treatment of cartilage cells with VAPs maintained their normal phenotype, inhibited matrix metalloproteinases (MMPs) secretion, kept the balance of cartilage matrix metabolism, and sustained an external environment where the cartilage cells could survive. Moreover, VAPs reduced the proportion of early apoptotic cells, suggesting that they may block the apoptotic pathway in OCs.

[Effects of Huanglian Jiedu Decoction on blood lipid metabolism and its related gene expressions in rats with hyperlipidemia].

OBJECTIVE: To observe the effects of Huanglian Jiedu Decoction (HJD), a compound traditional Chinese herbal medicine, on lipid metabolism and its related gene expressions in rats with hyperlipidemia. METHODS: Fifty SD rats were randomly divided into normal control group, untreated group, Lipitor (atorvastatin) group, and low- and high-dose HJD groups. Except the normal control group, rats in the other groups were fed with high-fat diet to induce hyperlipidemia. Then the rats were administered with corresponding drugs for 8 weeks. After treatment, the serum levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assayed. The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver tissues were measured. Low-density lipoprotein receptor (LDLR) and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expressions in liver tissues were determined by reverse transcription-polymerase chain reaction. RESULTS: Compared with the normal control group, the levels of serum TC, TAG and LDL-C in the untreated group were increased and the level of serum HDL-C was reduced. The activities of LPL and HL and expressions of LDLR and PPARgamma mRNAs in the untreated group were lower than those in the normal control group. After treatment, high-dose HJD significantly improved hyperlipemia by decreasing TC, TAG and LDL-C and increasing HDL-C. The activities of LPL and HL and expression levels of LDLR and PPARgamma mRNAs in liver tissues were also markedly enhanced in the high-dose HJD group as compared with those in the untreated group. CONCLUSION: HJD can activate the activity of lipid metabolism enzyme, and enhance the expressions of LDLR and PPARgamma mRNAs to modulate the lipid metabolic disorders in rats with hyperlipidemia.