Research progress of targeted therapy regulating Th17/Treg balance in bone immune diseases.

Rheumatoid arthritis (RA) and postmenopausal osteoporosis (PMOP) are common bone-immune diseases. The imbalance between helper (Th17) and regulatory T cells (Tregs) produced during differentiation of CD4+ T cells plays a key regulatory role in bone remodelling disorders in RA and PMOP. However, the specific regulatory mechanism of this imbalance in bone remodelling in RA and PMOP has not been clarified. Identifying the regulatory mechanism underlying the Th17/Treg imbalance in RA and PMOP during bone remodelling represents a key factor in the research and development of new drugs for bone immune diseases. In this review, the potential roles of Th17, Treg, and Th17/Treg imbalance in regulating bone remodelling in RA and PMOP have been summarised, and the potential mechanisms by which probiotics, traditional Chinese medicine compounds, and monomers maintain bone remodelling by regulating the Th17/Treg balance are expounded. The maintenance of Th17/Treg balance could be considered as an therapeutic alternative for the treatment of RA and PMOP. This study also summarizes the advantages and disadvantages of conventional treatments and the quality of life and rehabilitation of patients with RA and PMOP. The findings presented her will provide a better understanding of the close relationship between bone immunity and bone remodelling in chronic bone diseases and new ideas for future research, prevention, and treatment of bone immune diseases.

Research Progress on the Mechanism of the SFRP-Mediated Wnt Signalling Pathway Involved in Bone Metabolism in Osteoporosis.

Osteoporosis (OP) is a metabolic bone disease linked to an elevated fracture risk, primarily stemming from disruptions in bone metabolism. Present clinical treatments for OP merely alleviate symptoms. Hence, there exists a pressing need to identify novel targets for the clinical treatment of OP. Research indicates that the Wnt signalling pathway is modulated by serum-secreted frizzled-related protein 5 (SFRP5), potentially serving as a pivotal regulator in bone metabolism disorders. Moreover, studies confirm elevated SFRP5 expression in OP, with SFRP5 overexpression leading to the downregulation of Wnt and ß-catenin proteins in the Wnt signalling pathway, as well as the expression of osteogenesis-related marker molecules such as RUNX2, ALP, and OPN. Conversely, the opposite has been reported when SFRP5 is knocked out, suggesting that SFRP5 may be a key factor involved in the regulation of bone metabolism via the Wnt signalling axis. However, the molecular mechanisms underlying the action of SFRP5-induced OP have yet to be comprehensively elucidated. This review focusses on the molecular structure and function of SFRP5 and the potential molecular mechanisms of the SFRP5-mediated Wnt signalling pathway involved in bone metabolism in OP, providing reasonable evidence for the targeted therapy of SFRP5 for the prevention and treatment of OP.

Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.

Metabolic reprogramming is an adaptive response of tumour cells under hypoxia and low nutrition conditions. There is increasing evidence that glucose metabolism reprogramming can regulate the growth and metastasis of osteosarcoma (OS). Reprogramming in the progress of OS can bring opportunities for early diagnosis and treatment of OS. Previous research mainly focused on the glycolytic pathway of glucose metabolism, often neglecting the tricarboxylic acid cycle and pentose phosphate pathway. However, the tricarboxylic acid cycle and pentose phosphate pathway of glucose metabolism are also involved in the progression of OS and are closely related to this disease. The research on glucose metabolism in OS has not yet been summarized. In this review, we discuss the abnormal expression of key molecules related to glucose metabolism in OS and summarize the glucose metabolism related signaling pathways involved in the occurrence and development of OS. In addition, we discuss some of the targeted drugs that regulate glucose metabolism pathways, which can lead to effective strategies for targeted treatment of OS.

New insight of the pathogenesis in osteoarthritis: the intricate interplay of ferroptosis and autophagy mediated by mitophagy/chaperone-mediated autophagy.

Ferroptosis, characterized by iron accumulation and lipid peroxidation, is a form of iron-driven cell death. Mitophagy is a type of selective autophagy, where degradation of damaged mitochondria is the key mechanism for maintaining mitochondrial homeostasis. Additionally, Chaperone-mediated autophagy (CMA) is a biological process that transports individual cytoplasmic proteins to lysosomes for degradation through companion molecules such as heat shock proteins. Research has demonstrated the involvement of ferroptosis, mitophagy, and CMA in the pathological progression of Osteoarthritis (OA). Furthermore, research has indicated a significant correlation between alterations in the expression of reactive oxygen species (ROS), adenosine monophosphate (AMP)-activated protein kinase (AMPK), and hypoxia-inducible factors (HIFs) and the occurrence of OA, particularly in relation to ferroptosis and mitophagy. In light of these findings, our study aims to assess the regulatory functions of ferroptosis and mitophagy/CMA in the pathogenesis of OA. Additionally, we propose a mechanism of crosstalk between ferroptosis and mitophagy, while also examining potential pharmacological interventions for targeted therapy in OA. Ultimately, our research endeavors to offer novel insights and directions for the prevention and treatment of OA.

Advances in understanding effects of miRNAs on apoptosis, autophagy, and pyroptosis in knee osteoarthritis.

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs. MicroRNAs-mediated signaling pathways play a critical regulatory role in inducing apoptosis, autophagy, and pyroptosis in developing knee osteoarthritis (KOA). Given this, we searched databases, such as PubMed, using keywords including "miRNA," "knee osteoarthritis," "apoptosis," "autophagy," "pyroptosis", and their combinations. Through an extensive literature review, we conclude that miRNAs can be modulated through various signaling pathways, such as Wnt/ß-catenin, TGF-ß, PI3K/AKT/mTOR, and NLRP3/Caspase-1, to regulate apoptosis, autophagy, and pyroptosis in KOA. Furthermore, we note that P2X7R and HMGB1 may be crucial regulatory molecules involved in the interconnected regulation of apoptosis, autophagy, and pyroptosis in KOA. Additionally, we describe that miR-140-5p and miR-107 can modulate the advancement of KOA chondrocytes by targeting distinct molecules involved in apoptosis, autophagy, and pyroptosis, respectively. Therefore, we conclude that miRNAs may be potential biomarkers and therapeutic targets for the early prediction, diagnosis, and effective therapeutic approaches of KOA.

The mechanism of dendritic cell-T cell crosstalk in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint pain and swelling, synovial hyperplasia, cartilage damage, and bone destruction. The mechanisms of dendritic cell (DC) and T cell-mediated crosstalk have gradually become a focus of attention. DCs regulate the proliferation and differentiation of CD4+ T cell subtypes through different cytokines, surface molecules, and antigen presentation. DC-T cell crosstalk also blocks antigen presentation by DCs, ultimately maintaining immune tolerance. DC-T cell crosstalk mainly involves chemokines, surface molecules (TonEBP, NFATc1), the PD-L1/PD-1 signalling axis, and the TGF-ß signalling axis. In addition, DC-T cell crosstalk in RA is affected by glycolysis, reactive oxygen species, vitamin D, and other factors. These factors lead to the formation of an extremely complex regulatory network involving various mechanisms. This article reviews the key immune targets of DC-T cell crosstalk and elucidates the mechanism of DC-T cell crosstalk in RA to provide a basis for the treatment of patients with RA.

Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

Research progress on the role of lncRNA-miRNA networks in regulating adipogenic and osteogenic differentiation of bone marrow mesenchymal stem cells in osteoporosis.

Osteoporosis (OP) is characterized by a decrease in osteoblasts and an increase in adipocytes in the bone marrow compartment, alongside abnormal bone/fat differentiation, which ultimately results in imbalanced bone homeostasis. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts and adipocytes to maintain bone homeostasis. Several studies have shown that lncRNAs are competitive endogenous RNAs that form a lncRNA-miRNA network by targeting miRNA for the regulation of bone/fat differentiation in BMSCs; this mechanism is closely related to the corresponding treatment of OP and is important in the development of novel OP-targeted therapies. However, by reviewing the current literature, it became clear that there are limited summaries discussing the effects of the lncRNA-miRNA network on osteogenic/adipogenic differentiation in BMSCs. Therefore, this article provides a review of the current literature to explore the impact of the lncRNA-miRNA network on the osteogenic/adipogenic differentiation of BMSCs, with the aim of providing a new theoretical basis for the treatment of OP.

Network regulatory mechanism of ncRNA on the Wnt signaling pathway in osteoporosis.

Non-coding RNA (ncRNA) is a type of non-protein-coding RNA molecule transcribed from the genome which performs broad regulation of a variety of biological functions in human cells. The Wnt signaling pathway is highly conserved in multicellular organisms, playing an important role in their growth and development. Increasing evidence suggests that ncRNA can regulate cell biological function, enhance bone metabolism, and maintain normal bone homeostasis by interacting with the Wnt pathway. Studies have also demonstrated that the association of ncRNA with the Wnt pathway may be a potential biomarker for the diagnosis, evaluation of prognosis, and treatment of osteoporosis. The interaction of ncRNA with Wnt also performs an important regulatory role in the occurrence and development of osteoporosis. Targeted therapy of the ncRNA/Wnt axis may ultimately be the preferred choice for the treatment of osteoporosis in the future. The current article reviews the mechanism of the ncRNA/Wnt axis in osteoporosis and reveals the relationship between ncRNA and Wnt, thereby exploring novel molecular targets for the treatment of osteoporosis and providing theoretical scientific guidance for its clinical treatment.

Mitochondrial quality control and its role in osteoporosis.

Mitochondria are important organelles that provide cellular energy and play a vital role in cell differentiation and apoptosis. Osteoporosis is a chronic metabolic bone disease mainly caused by an imbalance in osteoblast and osteoclast activity. Under physiological conditions, mitochondria regulate the balance between osteogenesis and osteoclast activity and maintain bone homeostasis. Under pathological conditions, mitochondrial dysfunction alters this balance; this disruption is important in the pathogenesis of osteoporosis. Because of the role of mitochondrial dysfunction in osteoporosis, mitochondrial function can be targeted therapeutically in osteoporosis-related diseases. This article reviews different aspects of the pathological mechanism of mitochondrial dysfunction in osteoporosis, including mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy, and highlights targeted therapy of mitochondria in osteoporosis (diabetes induced osteoporosis and postmenopausal osteoporosis) to provide novel targets and prevention strategies for the prevention and treatment of osteoporosis and other chronic bone diseases.

Research Progress of Ferroptosis Regulatory Network and Bone Remodeling in Osteoporosis.

Ferroptosis was induced the programmed cell death with iron overload Fenton reaction. Currently, ferroptosis has not been studied thoroughly. Existing studies have confirmed that ferroptosis involves the metabolisms of the Fe, lipids, amino acid, each mechanism is mutually independent but interrelated, and they are formed a complex regulatory network. Other evidence supports that ferroptosis is participated osteoporotic bone remodeling, predominantly affecting the interaction between bone formation and bone resorption, explicitly bone resorption exceeded bone formation. Based on previous studies, this review will summarize the regulatory network mechanism of ferroptosis on bone remodeling and reveal the role of ferroptosis in osteoporosis (OP).

Zhongfeng Capsules protects against cerebral ischemia-reperfusion injury via mediating the phosphoinositide 3-kinase/Akt and toll-like receptor 4/nuclear factor kappa B signaling pathways by regulating neuronal apoptosis and inflammation.

Inflammatory reaction and neuronal apoptosis are the major pathophysiological mechanisms involved in cerebral ischemia-reperfusion injury (CI/RI). It has been reported that Zhongfeng Capsules (ZFCs), which contain Panax notoginseng, Hirudo, Red ginseng, Eupolyphaga sinensis, Pangolin scales, Rhubarb, and Radix Salvia miltiorrhizae, have a definite therapeutic effect on CI/RI. However, the specific molecular mechanisms of ZFCs are unclear. In this study, the effects of ZFCs on middle cerebral artery occlusion were investigated in rats. Our results showed that neurological impairment and neuronal apoptosis were alleviated in ZFC-treated rats. Additionally, infarct volume and cerebral edema decreased and there was an improvement in histopathological features. Furthermore, the expression levels of IL-1ß, IL-6, and TNF-α were downregulated in ZFC-treated rats. TLR 4, NF-κB, Bax, and Caspase-3 expression also tended to decrease, whereas the expression of Bcl-2, p-PI3K, p-Akt, and I-κBα increased. The results indicate that the ZFCs effectively protected the rats against CI/RI possibly via the TLR4/NF-κB signaling pathway. Additionally, the formulation regulated the transcriptional activity of NF-κB, secretion of downstream inflammatory factors, and the expression of Bcl-2-Bax proteins in the PI3K/Akt pathway. Our findings suggest that ZFCs suppress neuronal apoptosis and inflammatory reaction via the PI3K/Akt and TLR4/NF-κB signaling pathways, respectively. Moreover, activation of the PI3K/Akt pathway may result in the inhibition of proinflammatory cytokine secretion, which may be another mechanism by which ZFCs alleviate CI/RI.

[Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury].

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model.

BACKGROUND: Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice METHODS: The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured RESULTS: There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) CONCLUSIONS: This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.

[Wenweishu Capsule alleviates gastric mucosal lesion in rats with chronic gastritis by inhibiting NF-κB pathway].

Objective To investigate the effect of Wenweishu Capsule on the expression of nuclear factor kappa B (NF-κB)-related proteins in chronic gastritis model rats. Methods Wistar rat models of chronic gastritis were constructed by alternant administrations of sodium deoxycholate, ammonia, alcohol solution and the hunger disorder method. The rats were randomly divided into control group, model group, vatacoenayme group, high-, middle- and low-dose Wenweishu Capsule groups. The control group and model group were treated with normal saline (2 mL/d). The other groups were separately treated with 0.3 g/kg vatacoenayme and 0.76, 0.38, 0.19 g/kg Wenweishu Capsule for 4 weeks. Naked eye observation and HE staining were used to evaluate the pathological changes of gastric tissue. ELISA was performed to measure the levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the serum. Immunofluorescence staining was employed to observe the expression of NF-κBp65, inhibitor of NF-κBα (IκBα) in the gastric tissue. Simple Western was utilized to detect the protein levels of NF-κBp65, IκBα and COX2 in the gastric tissue. Results Compared with the control group, the model group was found with thinner gastric mucosa, disappeared or shallower folds, obviously infiltrated mucosa inflammatory cells, disordered glands, and significantly increased levels of serum inflammatory cytokines and NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Compared with the model group, the vatacoenayme group, high- and middle-dose Wenweishu Capsule groups showed the alleviated gastric cavity signs, improved histopathological changes, reduced levels of TNF-α and IL-6 in the serum, and decreased expression of NF-κBp65, IκBα and COX2 proteins in the gastric tissue. Conclusion Wenweishu Capsule can reduce the levels of serum inflammatory factors by inhibiting NF-κB pathway in the gastric tissue, so as to alleviate the injury of gastric mucosa in rats with chronic gastritis.

[Intervention effect of Youguiwan on rats with knee osteoarthritis and its mechanism].

Objective: To study the effects of Youguiwan on the osteoglycin (OGN), osteonectin (ON), fibrinogen 2 (FBN2) of articular cartilage tissue in the model of knee osteoarthritis (KOA). Methods: Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group, Youguiwan (high-dose, middle-dose and low-dose )group. The modified Hulth method was used to establish KOA models for 6 weeks. The sham control group and the model group were treated with normal saline. The rats in Youguiwan high-dose, middle-dose, low-dose groups were treated with Youguiwan at the doses of 4.8, 2.4, 1.2 g/kg by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g/kg. The rats were administrated for 8 weeks according to the dose. After intervening, articular cartilage of rats were obtained, the pathological changes were observed by using HE staining method, and Mankin score was evaluated. The expressions of OGN, ON and FBN2 in articular cartilage were detected by immunohistochemistry. The expression of GSK-3ß in articular cartilage was detected by Western blot. Results: Compared with the sham control group, the Mankin score was obviously increased in the model group, the protein expression of FBN2 was increased significantly, yet the protein expressions of OGN, ON and GSK-3ß were decreased significantly (P＜0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Mankin score was declined obviously in the high-dose Youguiwan group, the protein expression of FBN2 was significantly decreased, but the protein expression of GSK-3ß was significantly increased, the protein expressions of OGN and ON were significantly increased in the middle-dose and high-dose Youguiwan group (P＜0.05 or P＜0.01), cartilage structure was tended to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. Conclusion: Youguiwan can significantly improve the articular cartilage degeneration of KOA rats, its mechanism maybe raise OGN and ON protein expression level to promote the ossification and reconstruction of articular cartilage.

Zhengganxifeng Decoction Affects Gut Microbiota and Reduces Blood Pressure via Renin-Angiotensin System.

Zhengganxifeng decoction (ZGXFD) is a traditional Chinese medicinal formula, from "Medical Zhong parameter West recorded" by Xichun Zhang, which has been applied to the treatment of clinical essential hypertension. Besides its effect in blood pressure reduction, ZGXFD is also known to be a radical therapy with little or no side effects. Compared with western medicines, Chinese medicinal formulas have the advantage of simultaneously attacking multiple targets. However, such a property brings trouble to the pharmacological studies of Chinese medicines. This study investigated the composition of gut microbiota in spontaneously hypertensive rats (SHR) treated with ZGXFD. ZGXFD was shown to cause similar effects in the treatment group as benazepril: both were able to reduce in SHR the microbial diversity, Firmicutes to Bacteroidetes (F/B) ratio and coccus to bacillus (C/B) ratio. Meanwhile, ZGXFD can maintain the integrity of intestinal mechanistic barrier and elevate the percentage of bacteria producing short chain fatty acids (SCFA). By investigating renin-angiotensin system (RAS) system, we found that ZGXFD can decrease the expression of angiotensin-converting-enzyme (ACE) in lungs, which in turn causes a increase in AngI produces angiotensin1-7 (Ang1-7) and decrease in AngII. ZGXFD regulate blood pressure in SHR via RAS.

The Effects of Astragalus Polysaccharide on Bone Marrow-Derived Mesenchymal Stem Cell Proliferation and Morphology Induced by A549 Lung Cancer Cells.

BACKGROUND The tumor microenvironment in lung cancer plays an important role in tumor progression and metastasis. Bone marrow-derived mesenchymal stem cells (MSCs) co-cultured with A549 lung cancer cells show changes in morphology, increase cell proliferation, and cell migration. This study aimed to investigate the effects of Astragalus polysaccharide (APS), a traditional Chinese herbal medicine, on the changes induced in bone marrow-derived MSCs by A549 lung cancer cells in vitro. MATERIAL AND METHODS Bone marrow-derived MSCs were co-cultured with A549 cells (Co-BMSCs). Co-cultured bone marrow-derived MSCs and A549 cells treated with 50 µg/ml of APS (Co-BMSCs + APS) were compared with untreated Co-BMSCs. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay. Flow cytometry evaluated the cell cycle. Microarray assays for mRNA expression and Western blot for protein expression were used. RESULTS Compared with untreated Co-BMSCs, APS treatment of Co-BMSCs improved cell morphology, reduced cell proliferation, and inhibited cell cycle arrest. The mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappaB) pathway, TP53, caspase-3, acetylated H4K5, acetylated H4K8, and acetylated H3K9 were involved in the regulatory process. CONCLUSIONS APS treatment reduced cell proliferation and morphological changes in bone marrow-derived MSCs that were co-cultured with A549 lung cancer cells in vitro.

Effects of zoledronic acid and ibandronate in the treatment of cancer pain in rats with lung cancer combined with bone metastases.

The aim of the study was to investigate the efficiency and safety of zoledronic acid and ibandronate in the treatment of rats with lung cancer combined with bone metastases. A total of 124 rats with lung cancer bone metastasis were established. Rats were randomly divided into A, B and C groups (n=30). Rats in group A were treated with ibandronate combined with zoledronic acid, rats in group B were treated with zoledronic acid monotherapy, and rats in group C were treated with ibandronate monotherapy. Rats in group A were injected subcutaneously with zoledronic acid 0.1 mg/kg and ibandronate 10 µg/kg, once per week for 12 weeks; rats in group B were injected subcutaneously with zoledronic acid, and rats in group C were injected subcutaneously with ibandronate, the same method as the treatment group. The remaining 34 SD rats were not treated to serve as the control group. Treatment efficacy and physical improvement in 8 weeks were observed, and improvement of pain behavior in rats was evaluated to reflect the effect of drug treatment. Of the 30 rats in group A, 25 showed different degrees of remission, 5 rats showed no improvement and the effective rate was 83.3%. Of the 30 rats in group B, 21 showed different degrees of remission, 9 rats showed no improvement and the effective rate was 70%. Of the 30 rats in group C, 20 showed different degrees of remission, 10 rats showed no improvement and the effective rate was 66.7%. Statistically significant differences in total effective rate were found among three groups, and the combined method showed the highest effective rate (P<0.05). Ibandronate combined with zoledronic acid has a good therapeutic effect on cancer pain caused by bone metastases from lung cancer.