Signaling pathways in hair aging

Hair follicle (HF) homeostasis is regulated by various signaling pathways. Disruption of such homeostasis leads to HF disorders, such as alopecia, pigment loss, and hair aging, which is causing severe health problems and aesthetic concerns. Among these disorders, hair aging is characterized by hair graying, hair loss, hair follicle miniaturization (HFM), and structural changes to the hair shaft. Hair aging occurs under physiological conditions, while premature hair aging is often associated with certain pathological conditions. Numerous investigations have been made to determine the mechanisms and explore treatments to prevent hair aging. The most well-known hypotheses about hair aging include oxidative stress, hormonal disorders, inflammation, as well as DNA damage and repair defects. Ultimately, these factors pose threats to HF cells, especially stem cells such as hair follicle stem cells, melanocyte stem cells, and mesenchymal stem cells, which hamper hair regeneration and pigmentation. Here, we summarize previous studies investigating the above mechanisms and the existing therapeutic methods for hair aging. We also provide insights into hair aging research and discuss the limitations and outlook

Survey on Aerial Manipulator: System, Modeling, and Control

The aerial manipulator is a special and new type of flying robot composed of a rotorcraft unmanned aerial vehicle (UAV) and a/several manipulator/s. It has gained a lot of attention since its initial appearance in 2010. This is mainly because it enables traditional UAVs to conduct versatile manipulating tasks from air, considerably enriching their applications. In this survey, a complete and systematic review of related research on this topic is conducted. First, various types of structure designs of aerial manipulators are listed out. Subsequently, the modeling and control methods are introduced in detail from the perspective of two types of typical application cases: free-flight and motion-restricted operations. Finally, challenges for future research are presented

MFG-E8 promotes M2 polarization of macrophages and is associated with poor prognosis in patients with gastric cancer

Background: Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) has been reported to play an oncogenic role in a variety of tumors. However, its involvement in gastric cancer (GC) development has not been described. Methods: The cancer genome atlas (TCGA) and the gene expression omnibus database (GEO) databases were used to analyze the expression of MFG-E8 in GC. These findings were further validated using immunohistochemistry (IHC) and western blotting assay (WB). Kaplan-Meier method, univariate logistic regression, and Christopher Cox regression were used to study the relationship between MFG-E8 and clinical pathology. In addition, the potential signaling pathways involved in MFG-E8 and its potential correlation with levels of immune cell infiltration were investigated. Finally, the biological function of MFG-E8 in GC cells was revealed. Results: MFG-E8 was highly expressed in GC patients and cells, and the high level of MFG-E8 was associated with poor overall survival (OS). KEGG analysis indicated that MFG-E8 may play an important role in the cAMP signaling pathway. The expression of MFG-E8 was positively correlated with the infiltration of M2 macrophages. The patients with high MFG-E8 were easy to develop chemotherapy resistance. Furthermore, the knockdown of MFG-E8 significantly inhibited the proliferation and invasion of GC cells. Conclusion: MFG-E8 in GC may serve as a prognostic marker and a potential immunotherapy target for GC

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Abstract Background Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. Methods Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). Results A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49–0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. Conclusions Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. Trial registration The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014