The role of autophagy in the treatment of osteoporosis by Chinese medicines (natural)

Osteoporosis is one of the common orthopaedic diseases, characterised by increased bone fragility due to reduced bone mass and microstructural degeneration, posing a great threat to patients’ quality of life and safety. In recent years, Chinese medicine (natural) has had a unique advantage in the treatment of osteoporosis and has shown good efficacy. Autophagy is an inherent cellular survival mechanism for the removal and recycling of damaged proteins and organelles and plays an important role in maintaining the stability of the intracellular environment and organ function. Therefore, this article aims to provide a comprehensive review of these Chinese medicines (natural) for the treatment of osteoporosis through autophagy. They have been intensively studied and reported to have effects such as promoting osteogenesis and anti-bone resorption. The Chinese medicines include plants such as Cistanche deserticola, Epimedium, Curculigo orchioides Gaertn, Achyranthes bidentata Blume, Leonurus japonicus Houtt, Ginseng, Chuanxiong Rhizome, Eucommia ulmoides, Morindae Officinalis Radix, Curcuma longa, Polygoni Cuspidati Rhizoma et Radix, Anemarrhena asphodeloides Bunge, Salvia miltiorrhiza Bge and Pueraria Lobata, thus providing evidence for the use of alternative herbal therapies for the effective treatment of osteoporosis

Identification of copper death-associated molecular clusters and immunological profiles in rheumatoid arthritis

Objective: An analysis of the relationship between rheumatoid arthritis (RA) and copper death-related genes (CRG) was explored based on the GEO dataset. / Methods: Based on the differential gene expression profiles in the GSE93272 dataset, their relationship to CRG and immune signature were analysed. Using 232 RA samples, molecular clusters with CRG were delineated and analysed for expression and immune infiltration. Genes specific to the CRGcluster were identified by the WGCNA algorithm. Four machine learning models were then built and validated after selecting the optimal model to obtain the significant predicted genes, and validated by constructing RA rat models. / Results: The location of the 13 CRGs on the chromosome was determined and, except for GCSH. LIPT1, FDX1, DLD, DBT, LIAS and ATP7A were expressed at significantly higher levels in RA samples than in non-RA, and DLST was significantly lower. RA samples were significantly expressed in immune cells such as B cells memory and differentially expressed genes such as LIPT1 were also strongly associated with the presence of immune infiltration. Two copper death-related molecular clusters were identified in RA samples. A higher level of immune infiltration and expression of CRGcluster C2 was found in the RA population. There were 314 crossover genes between the 2 molecular clusters, which were further divided into two molecular clusters. A significant difference in immune infiltration and expression levels was found between the two. Based on the five genes obtained from the RF model (AUC = 0.843), the Nomogram model, calibration curve and DCA also demonstrated their accuracy in predicting RA subtypes. The expression levels of the five genes were significantly higher in RA samples than in non-RA, and the ROC curves demonstrated their better predictive effect. Identification of predictive genes by RA animal model experiments was also confirmed. / Conclusion: This study provides some insight into the correlation between rheumatoid arthritis and copper mortality, as well as a predictive model that is expected to support the development of targeted treatment options in the future

Gujin Dan is a Chinese medicine formulation that stimulates cell proliferation and differentiation by controlling multiple genes involved in MC3T3-E1 cells

Background: With the development of Traditional Chinese medicine (TCM) in recent years, the use of TCM in the treatment of osteoporosis has received much attention and research. Gujin Dan (GJD) is one of the representative Chinese medicine formulations that work synergistically with 19 herbs and has been used for decades to treat cervical spondylosis, lumbar disc herniation, osteoarthritis and osteoporosis. However, the exact molecular mechanism by which GJD is used to strengthen bones in the treatment of osteoporosis remains largely unknown. / Methods: In this study, an aqueous extract of GJD was prepared and its components were identified by high-performance liquid chromatography (HPLC). The effect of GJD aqueous extract on MC3T3-E1 cells was determined by Cell Counting Kit-8 (CCK-8) assay, alkaline phosphatase (ALP), and alizarin red S staining (ARS), combined with RNA sequencing (RNA-seq) and qRT-PCR. / Results: Our study showed that GJD significantly promoted the proliferation of MC3T3-E1 cells, as well as the synthesis and mineralisation of the extracellular matrix. GJD significantly increased the expression levels of genes that promote cell proliferation such as Adamts1, Mcam, Cyr61, Fos, Cebpd, Fosl2, Sirt1, Nipbl, Sema3c and Kcnq1ot1, up-regulated genes that inhibit apoptosis such as Gadd45a, Birc3, up-regulated genes that inhibit osteoclastogenesis such as Bcl6, Nfkbiz, Clcf1, Bcl3, Lgals3, Wisp1, Dusp1 and Fblim1, up-regulated genes that promote MC3T3-E1 cell differentiation such as Junb, Egr1, Klf10, Atf6, Malat1, Btg2, Sertad4, Zfyve16, Tet2, Creb5, Snai2, Fam46a, Calcrl and Pdzrn3. In addition, GJD mildly upregulated the expression levels of gene markers such as Atf4, Fn1, Usp7, Sox4, Col16a1, Spp1, Bmp1, Runx2, Bglap, Col12a1, and Alpl in osteoblasts. / Conclusions: Our results show that GJD promotes the differentiation and proliferation of MC3T3-E1 cells, inhibits osteoclast formation, and prevents osteoblast apoptosis. The present study significantly improves the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides a new strategy for the further use of Chinese medicinal preparations against bone metabolism-related diseases

Optimal algorithms for single-machine scheduling with rejection to minimize the makespan

In this paper we consider the single-machine scheduling problem with rejection. Each job has an arrival time, a processing time and a rejection penalty. The objective is to minimize the sum of the makespan of the accepted jobs and the total rejection penalty of the rejected jobs. First, we present a polynomial-time algorithm for the off-line problem when split is allowed. Second, for the on-line problem with arbitrary arrival times, we provide a determined on-line algorithm with the best-possible competitive ratio 2. Finally, for the on-line problem with at most two distinct arrival times, we provide a determined on-line algorithm with the best-possible competitive ratio .Scheduling Rejection penalty On-line algorithm Competitive ratio

Prediction of the Molecular Mechanism of Corni Fructus-Epimedii Folium-Rehmanniae Radix Praeparata in the Treatment of Postmenopausal Osteoporosis Based on Network Pharmacology and Molecular Docking

INTRODUCTION: In this study, core drugs of clinical postmenopausal osteoporosis were retrieved using data mining, the drug molecular action target was predicted through network pharmacology, the key nodes of interaction were identified by combining postmenopausal osteoporosis-related targets, and the pharmacological mechanism of Traditional Chinese Medicine (TCM) against postmenopausal osteoporosis and other action mechanisms was explored. METHODS: TCMISS V2.5 was used to collect TCM prescriptions of postmenopausal osteoporosis from databases, including Zhiwang, Wanfang, PubMed, etc., for selecting the highest confidence drugs. TCMSP and SwissTargetPrediction databases were selected to screen the main active ingredients of the highest confidence drugs and their targets. Relevant targets for postmenopausal osteoporosis were retrieved from GeneCards and GEO databases, PPI network diagrams construction and selection of core nodes in the network, GO and KEGG enrichment analysis, and molecular docking validation. RESULTS: Correlation analysis identified core drug pairs as 'Corni Fructus-Epimedii Folium-Rehmanniae Radix Praeparata' (SZY-YYH-SDH). After TCMSP co-screening and de-weighting, 36 major active ingredients and 305 potential targets were selected. PPI network graph was built from the 153 disease targets and 24 TCM disease intersection targets obtained. GO, KEGG enrichment results showed that the intersectional targets were enriched in the PI3K-Akt signalling pathway, etc. The target organs were mainly distributed in the thyroid, liver, CD33+_Myeloid, etc. Molecular docking results showed that the core active ingredients of the 'SZY-YYH-SDH' were able to bind to the pair core nodes and PTEN and EGFR. CONCLUSION: The results showed that 'SZY-YYH-SDH' can provide the basis for clinical application and treat postmenopausal osteoporosis through multi-component, multi-pathway, and multi-target effects

Family Income Affects Children’s Altruistic Behavior in the Dictator Game

This study aimed to examine how family income and social distance influence young rural Chinese children’s altruistic behavior in the dictator game (DG). A total of 469 four-year-old children from eight rural areas in China, including many children left behind by parents who had migrated to urban areas for work, played the DG. Stickers comprised the resource, while recipients in the game were assumed to be either their friends or strangers, with the social distance (i.e., strangers compared to friends) as a between-subjects variable. Children donated significantly more stickers to their friends than to strangers. Moreover, children from lower income families donated more stickers than children from higher income families. However, no gender and parental migrant status differences in children’s prosocial behaviors were evident in this sample. Findings of this study suggest that children’s altruistic behaviours to peers are influenced by family characteristics since preschool age. The probable influence of local socialization practices on development and the possible adaptive significance were discussed