Chronic Alcohol Reduces Bone Mass Through Inhibiting Proliferation and Promoting Aging of Endothelial Cells in Type-H Vessels.

Alcohol consumption is regarded as one of the leading risk factors for secondary osteopenia. Angiogenesis and osteogenesis coupled by type-H vessels coordinate the biological process of bone homeostasis to prevent osteopenia. This study aimed to determine whether chronic alcohol inhibits type-H vessel-dependent bone formation.

PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice.

Alkylating agents (AAs) that are commonly used for cancer therapy cause great damage to the ovary. Pyrroloquinoline-quinine (PQQ), which was initially identified as a redox cofactor for bacterial dehydrogenases, has been demonstrated to benefit the fertility of females. The aim of this study was to investigate whether PQQ dietary supplementation plays a protective role against alkylating agent-induced ovarian dysfunction.

Amniotic membrane mesenchymal stem cells-based therapy improves Bmi-1-deficient mandible osteoporosis through stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption.

Mandible osteoporosis with age is characterized by greater fragility and accompanied with abnormal oral function. Mesenchymal stem cell transplantation can ameliorate osteoporosis. Bmi-1 is a transcriptional repressor which is an important regulator of cell cycle, stem cells self-renewal, and cell senescence.

Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB.

As an important hormone that regulates the balance of calcium and phosphorus, parathyroid hormone (PTH) has also been found to have an important function in intervertebral disc degeneration (IVDD). Our aim was to investigate the mechanism by which PTH alleviates IVDD. In this study, the PTH 1 receptor was found to be highly expressed in severely degenerated human nucleus pulposus (NP) cells.

Rebalance of the Polyamine Metabolism Suppresses Oxidative Stress and Delays Senescence in Nucleus Pulposus Cells.

Intervertebral disk degeneration (IDD) is a major cause of low back pain that becomes a prevalent age-related disease. However, the pathophysiological processes behind IDD are rarely known. Here, we used bioinformatics analysis based on the microarray datasets (GSE34095) to identify the differentially expressed genes (DEGs) as biomarkers and therapeutic targets in degenerated discs.

A Sonic Hedgehog-Gli-Bmi1 signaling pathway plays a critical role in p27 deficiency induced bone anabolism.

To explore the mechanism of the bone anabolic action of p27 deficiency, we first confirmed that osteoblast formation and osteogenesis were significantly increased in p27 deficient mice compared with their wild-type littermates. Microarray analysis of differential gene expression profiles, followed by real-time RT-PCR and Western blots revealed that p27 deletion significantly upregulated the expression of Sonic hedgehog (Shh), Gli1 and 2 and their target gene Bmi1 in bone tissue, and significantly down regulated the expression of the negative regulators of the Shh pathway Sufu, Patched 1 and Gli3 in bone tissue. The Shh antagonist KAAD-cyclopamine or vismodegib significantly reduced osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs) and osteoblastic bone formation .

Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis.

Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution. The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level. In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues.

1,25-Dihydroxyvitamin D deficiency induces sarcopenia by inducing skeletal muscle cell senescence.

To determine if 1,25(OH)D deficiency can induce age-related sarcopenia, the skeletal muscular phenotype of male wild-type (WT) and Cyp27b1 knockout (KO) mice were compared at 3 and 6 months of age. We found that muscle mass, grip strength and muscle fiber size were significantly decreased in aging Cyp27b1 KO male mice. The expression levels of genes related to mitochondrial metabolic activity, and antioxidant enzymes including SOD1, catalase, Nqo1 and Gcs were significantly down-regulated in skeletal muscle tissue of Cyp27b1 KO male mice; in contrast, the percentage of p16 and p21 myofibers, and the expression of p16, p19, p21, p53, TNFα, IL6 and MMP3 at mRNA and/or protein levels were significantly increased.

Inhibition of Nrf2 degradation alleviates age-related osteoporosis induced by 1,25-Dihydroxyvitamin D deficiency.

Previous studies have shown that 1,25(OH)D plays an anti-osteoporosis role by an anti-aging mechanism. Oxidative stress is a key mediator of aging and bone loss; however, whether 1,25(OH)D can exert its anti-osteoporosis effect by inhibiting oxidative stress is unclear. In this study, osteoporosis and the bone aging phenotype induced by 1,25(OH)D deficiency in male mice were significantly rescued in vivo upon the supplementation of oltipraz, an inhibitor of Nrf2 degradation.

P16 Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Deficiency.

This study aimed to determine whether deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from -deficient ( ), and double-knockout ( ), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16 and occludin.

Engineered exosomes for co-delivery of PGM5-AS1 and oxaliplatin to reverse drug resistance in colon cancer.

Oxaliplatin resistance inevitably occurs in almost all cases of metastatic colorectal cancer (CRC), and it is important to study the roles of lncRNAs and their specific regulatory mechanisms in oxaliplatin resistance. Exosomes are increasingly designed for drug or functional nucleic acid delivery due to their properties, thereby improving the effectiveness of cancer therapy. The results of this study show that the low expression of PGM5 antisense RNA 1 (PGM5-AS1) in colon cancer is induced by transcription inhibitor, GFI1B.

ELF3-AS1 contributes to gastric cancer progression by binding to hnRNPK and induces thrombocytosis in peripheral blood.

Numerous studies have reported that a variety of long noncoding RNAs (lncRNAs) can promote the proliferation, invasion, and migration of different tumor cells. However, different lncRNAs regulate cell functions in various forms, and the exact mechanisms are not clear. Here, we investigated the effect of the lncRNA ELF3-AS1 on gastric cancer (GC) cell function and explored the exact mechanism.

Pseudogene HSPA7 is a poor prognostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and correlated with immune infiltrates.

Background: Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer.

Methods: Firstly, we used Logistic regression, the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the expression level of HSPA7 in KIRC, then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival (OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters.

Erratum: CoQ10 suppression of oxidative stress and cell senescence increases bone mass in orchiectomized mice.

[This corrects the article on p. 4314 in vol. 12, PMID: 32913507.

The mechanism of pyrroloquinoline quinone influencing the fracture healing process of estrogen-deficient mice by inhibiting oxidative stress.

It is reported that oxidative stress plays a detrimental role in the process of bone fracture healing. And pyrroloquinoline quinone (PQQ) is used as antioxidant. However, there is no report about whether PQQ supplementation can promote fracture healing by eliminating oxidative stress.

Bmi1 regulate tooth and mandible development by inhibiting p16 signal pathway.

To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16-deficient (p16 ) mice, homozygous Bmi1-deficient (Bmi1 ) mice, double homozygous Bmi1 and p16-deficient (Bmi1 p16 ) mice to those of their wild-type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1 mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1 p16 mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice.

Elevated HB-EGF expression in neural stem cells causes middle age obesity by suppressing Hypocretin/Orexin expression.

Obesity is common in the middle aged population and it increases the risks of diabetes, cardiovascular diseases, certain cancers, and dementia. Yet, its etiology remains incompletely understood. Here, we show that ectopic expression of HB-EGF, an important regulator of neurogenesis, in Nestin neuroepithelial progenitors with the Cre-LoxP system leads to development of spontaneous middle age obesity in male mice accompanied by hyperglycemia and insulin resistance.

The Anatomic Features of Müller's Muscle: A Histology Study in Chinese.

Unlabelled: The purpose of this article is to clarify the character of Müller's muscle in Chinese specimens.

Methods: Ten upper eyelids of 10 formalin-fixed Chinese cadavers (9 elderly people, from 68 to 86 years of age; 1 male child, 10 years old) were examined. Full-thickness sagittal sections of the central part of the upper eyelids were microscopically examined using hematoxylin-eosin, Masson trichrome, and anti-smooth muscle actin antibodies staining.

AMH has no role in predicting oocyte quality in women with advanced age undergoing IVF/ICSI cycles.

It has been widely acknowledged that anti-Müllerian hormone (AMH) is a golden marker of ovarian reserve. Declined ovarian reserve (DOR), based on experience from reproductive-aged women, refers to both the quantitative and qualitative reduction in oocytes. This view is challenged by a recent study clearly showing that the quality of oocytes is similar in young women undergoing IVF cycles irrespective of the level of AMH.

CoQ10 suppression of oxidative stress and cell senescence increases bone mass in orchiectomized mice.

Numerous studies support the detrimental effects of oxidative stress and cell senescence on skeletal homeostasis. Coenzyme Q10 (CoQ10) acts as a scavenger for oxidative stress and protects mitochondrial activity from oxidative damage. However, it is unclear whether CoQ10 has a protective effect on osteoporosis caused by orchiectomy.

Exosomal Transfer of LCP1 Promotes Osteosarcoma Cell Tumorigenesis and Metastasis by Activating the JAK2/STAT3 Signaling Pathway.

Increasing evidence indicates that lymphocyte cytosolic protein 1 (LCP1) overexpression contributes to tumor progression; however, its role in osteosarcoma (OS) remains unclear. We aimed to investigate the potential effect of LCP1 in OS and the underlying mechanisms. We first demonstrated that LCP1 is upregulated in OS cell lines and tissues.

Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment.

The transcriptional repressor Bmi-1 is involved in cell-cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi-1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N-acetylcysteine (NAC) on intervertebral disc degeneration. Bmi-1 mice were treated with the antioxidant NAC, supplied in drinking water (Bmi-1 +NAC).

P27 deletion enhances hematopoiesis by paracrine action of IL22 secreted from bone marrow mesenchymal stem cells.

Previous studies have reported that p27 deletion stimulates the proliferation of bone marrow mesenchymal stem cells (BM-MSCs) and their differentiation into osteoblasts, it also increases bone marrow hematopoietic progenitor cells (HPCs). However, it is unknown whether the enhanced hematopoiesis induced by p27 deficiency was associated with releasing hematopoietic stem cell (HSC) and HPC supporting factors by BM-MSCs. To answer this question, we cultured the BM-MSCs from wild-type (WT) or p27 knockout (KO) mice, analyzed their proliferation, apoptosis and osteogenesis and harvested their conditioned medium (CM); We also cultured the bone marrow cells (BMCs) with normal medium or CM from WT or KO BM-MSCs and analyzed changes of HSCs and HPCs and colony forming cells (CFCs).

Suppression effect of N-acetylcysteine on bone loss in ovariectomized mice.

Oxidative stress can trigger DNA damage response and activation of cellular senescence. Accumulating studies have demonstrated that senescent cells can produce senescence-associated secretory phenotype that leads to increased bone resorption and decreased bone formation. And elimination of senescent cells or inhibition of SASP secretion has been shown to prevent bone loss in mice.