Inhibiting autophagy further promotes Ginkgolide B's anti-osteoclastogenesis ability.

Excessive osteoclast activity could cause skeletal diseases including osteoporosis. Additionally, autophagy plays an initial role in osteoclast differentiation and function. Ginkgolide B (GB), a key compound in Ginkgo biloba, improves bone mass and suppresses mature osteoclast formation in vitro.

Jekyll and Hyde leadership: Examining the direct and vicarious experiences of abusive and ethical leadership through a justice variability lens.

Drawing on uncertainty management theory and the nascent work on justice variability, we examine employees' and experiences of abusive supervision and ethical leadership. Conceptualizing the simultaneous display of abusive and ethical leadership styles as a form of justice variability, we suggest that a direct supervisor's ethical leadership exacerbates, rather than ameliorates, the detrimental effects of his/her abusive supervision on employees' emotional exhaustion and job performance. We further contend that a similar effect exists when employees vicariously experience leadership interactions involving their direct supervisor and higher level manager, whereby higher level managers' ethical leadership exacerbates the negative effects of their abusive supervision toward supervisors on those supervisors' employees' emotional exhaustion and job performance.

Urolithiasis Causes Osteoporosis in Asians: Genetic Evidence from Mendelian Randomization and Pathway Analysis.

Background: It is an indisputable fact that patients with urolithiasis are prone to osteoporosis (OP), but the specific mechanism of their association is unclear. Previous studies have focused on the mediation of environmental factors such as diet; however, the potential of urolithiasis itself to induce OP remains uncertain.

Methods: In this study, we used data from the Japan BioBank (6,638 urolithiasis and 7,788 OP cases) to investigate the direct causal relationship and mechanism between urolithiasis and OP, applying Mendelian randomization (MR), genetic correlation analysis, colocalization, and pathway analysis.

Mesenchymal stem cells shift the pro-inflammatory phenotype of neutrophils to ameliorate acute lung injury.

Background: Mesenchymal stem cell (MSC) treatment plays a major role in the management of acute lung injury (ALI), and neutrophils are the initial line of defense against ALI. However, the effect of MSCs on neutrophils in ALI remains mostly unknown.

Methods: We investigated the characteristics of neutrophils in lung tissue of ALI mice induced by lipopolysaccharide after treatment with MSCs using single-cell RNA sequencing.

Curcumin suppresses RANKL-induced osteoclast precursor autophagy in osteoclastogenesis by inhibiting RANK signaling and downstream JNK-BCL2-Beclin1 pathway.

Background: Curcumin ameliorates bone loss by inhibiting osteoclastogenesis. Curcumin inhibits RANKL-promoted autophagy in osteoclast precursors (OCPs), which mediates its anti-osteoclastogenic effect. But the role of RANKL signaling in curcumin-regulated OCP autophagy is unknown.

Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models.

Background: Although increasing preclinical studies have emphasized the benefits of exosome-related therapies, the efficacy of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) for liver injury is unclear. In this work, a pooled analysis was conducted to explore the overall effect of MSC-EV in animal models.

Methods: A systematic search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases was performed, from initiation to February 2022, for preclinical studies with liver disease models.

Characteristic Analysis of Featured Genes Associated with Cholangiocarcinoma Progression.

The noninvasive diagnosis of cholangiocarcinoma (CCA) is insufficiently accurate. Therefore, the discovery of new prognostic markers is vital for the understanding of the CCA mechanism and related treatment. The information on CCA patients in The Cancer Genome Atlas database was used for weighted gene co-expression network analysis.

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

Objective: In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial.

Methods: PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.

Erratum to "MiRNA-10b Reciprocally Stimulates Osteogenesis and Inhibits Adipogenesis Partly through the TGF-β/SMAD2 Signaling Pathway".

[This corrects the article on p. 1058 in vol. 9, PMID: 30574418.

The Impact of Family Care for the Elderly on Women's Employment from the Perspective of Bargaining Power.

Due to the wishes of the elderly and the traditional family culture in China, family care is the main way of providing for the aged, and women's care is the main way. This is not conducive to the protection of women's employment rights and the realization of self-worth under the background of increasing women's autonomy. Based on the latest data of the China Health and Nutrition Survey Database (CHNS), this paper uses ordinary least squares (OLS) and the instrumental variable method of control endogeneity to analyze the influence of family care activities on the labor participation rate of married women.

Long noncoding RNA LYPLAL1-AS1 regulates adipogenic differentiation of human mesenchymal stem cells by targeting desmoplakin and inhibiting the Wnt/β-catenin pathway.

Long noncoding RNAs are crucial factors for modulating adipogenic differentiation, but only a few have been identified in humans. In the current study, we identified a previously unknown human long noncoding RNA, LYPLAL1-antisense RNA1 (LYPLAL1-AS1), which was dramatically upregulated during the adipogenic differentiation of human adipose-derived mesenchymal stem cells (hAMSCs). Based on 5' and 3' rapid amplification of cDNA ends assays, full-length LYPLAL1-AS1 was 523 nt.

Lnc13728 facilitates human mesenchymal stem cell adipogenic differentiation via positive regulation of ZBED3 and downregulation of the WNT/β-catenin pathway.

Background: Obesity has received increasing attention because of its widespread worldwide occurrence and many threats to health. Human adipose-derived mesenchymal stem cells (hADSCs) are a critical source of adipocytes. Long noncoding RNAs (lncRNAs) play pivotal roles in cell fate determination and differentiation.

NITD-688, a pan-serotype inhibitor of the dengue virus NS4B protein, shows favorable pharmacokinetics and efficacy in preclinical animal models.

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to public health, yet no antiviral drug is available. We performed a high-throughput phenotypic screen using the Novartis compound library and identified candidate chemical inhibitors of DENV. This chemical series was optimized to improve properties such as anti-DENV potency and solubility.

A Cyclic Phosphoramidate Prodrug of 2'-Deoxy-2'-Fluoro-2'--Methylguanosine for the Treatment of Dengue Virus Infection.

Monophosphate prodrug analogs of 2'-deoxy-2'-fluoro-2'--methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue virus activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are among the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2'-deoxy-2'-fluoro-2'--methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration.

A novel long noncoding RNA, AC092834.1, regulates the adipogenic differentiation of human adipose-derived mesenchymal stem cells via the DKK1/Wnt/β-catenin signaling pathway.

Long noncoding RNAs (lncRNAs) have been implicated in a range of developmental processes and diseases, but the roles and mechanisms by which they act in adipogenic differentiation and adipose tissue biology are still unknown. By comparing the different expression patterns of lncRNAs before and after the adipocyte differentiation of human adipose-derived mesenchymal stem cells (hADSCs), we characterized a novel lncRNA, AC092834.1, which is significantly increased in preadipocytes.

Chlorzoxazone, a small molecule drug, augments immunosuppressive capacity of mesenchymal stem cells via modulation of FOXO3 phosphorylation.

Nowadays, immune diseases are a large burden in healthcare. Mesenchymal stem cells (MSCs) have prominent ability in immunomodulation and have been applicated on treating many immune-related diseases. However, the clinical outcomes can be disparate and sometimes completely counterproductive beyond explanation of cell heterogeneity.

Curcumin suppresses osteogenesis by inducing miR-126a-3p and subsequently suppressing the WNT/LRP6 pathway.

Curcumin, a natural phenolic biphenyl compound derived from the plant modulates multiple steps of carcinogenesis partly by affecting the expression of miRNAs. Interestingly, cancer development shares many of the same signalling pathways with bone formation. Reduced bone mass creates favourable conditions for tumor metastasis.

Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2.

The generation of definitive endoderm (DE) cells in sufficient numbers is a prerequisite for cell-replacement therapy for liver and pancreatic diseases. Previously, we reported that human adipose-derived mesenchymal stem cells (hAMSCs) can be induced to DE lineages and subsequent functional cells. Clarifying the regulatory mechanisms underlying the fate conversion from hAMSCs to DE is helpful for developing new strategies to improve the differentiation efficiency from hAMSCs to DE organs.

MiR-1292 Targets FZD4 to Regulate Senescence and Osteogenic Differentiation of Stem Cells in TE/SJ/Mesenchymal Tissue System via the Wnt/β-catenin Pathway.

With the expansion of the elderly population, age-related osteoporosis and the resulting bone loss have become a significant health and socioeconomic issue. In Triple Energizer (TE)/San Jiao (SJ)/mesenchymal tissue system, mesenchymal stem cell (MSC) senescence, and impaired osteogenesis are thought to contribute to age-related diseases such as osteoporosis. Therefore, comprehending the molecular mechanisms underlying MSC senescence and osteogenesis is essential to improve the treatment of bone metabolic diseases.

MiRNA-10b Reciprocally Stimulates Osteogenesis and Inhibits Adipogenesis Partly through the TGF-β/SMAD2 Signaling Pathway.

As the population ages, the medical and socioeconomic impact of age-related bone disorders will further increase. An imbalance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) can lead to various bone and metabolic diseases such as osteoporosis. Thus, understanding the molecular mechanisms underlying MSC osteogenic and adipogenic differentiation is important for the discovery of novel therapeutic paradigms for these diseases.

Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase.

To identify a potent and selective nucleoside inhibitor of dengue virus RNA-dependent RNA polymerase, a series of 2'- and/or 4'-ribose sugar modified uridine nucleoside phosphoramidate prodrugs and their corresponding triphosphates were synthesized and evaluated. Replacement of 2'-OH with 2'-F led to be a poor substrate for both dengue virus and human mitochondrial RNA polymerases. Instead of 2'-fluorination, the introduction of fluorine at the ribose 4'-position was found not to affect the inhibition of the dengue virus polymerase with a reduction in uptake by mitochondrial RNA polymerase.