SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction.

From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure.

-mutated NSCLC is Dependent on Tumor-secreted GDF15.

Cachexia is a wasting syndrome comprised of adipose, muscle, and weight loss observed in cancer patients. Tumor loss-of-function mutations in , a regulator of the energy sensor AMP-activated protein kinase, induce cancer cachexia (CC) in preclinical models and are associated with cancer-related weight loss in NSCLC patients. Here we characterized the relevance of the NSCLC-associated cachexia factor growth differentiation factor 15 (GDF15) in several patient-derived and genetically engineered -mutant NSCLC cachexia lines.

Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China.

Background: This study aimed to screen and validate noise-induced hearing loss (NIHL) associated single nucleotide polymorphisms (SNPs), construct genetic risk prediction models, and evaluate higher-order gene-gene, gene-environment interactions for NIHL in Chinese population.

Methods: First, 83 cases and 83 controls were recruited and 60 candidate SNPs were genotyped. Then SNPs with promising results were validated in another case-control study (153 cases and 252 controls).

Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity.

Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle.

CHAC1 inactivation is effective to preserve muscle glutathione but is insufficient to protect against muscle wasting in cachexia.

Muscle wasting is one of the main characteristics of cachexia associated with cancer and other chronic diseases and is often exacerbated by antineoplastic agents. Increased oxidative stress is associated with muscle wasting, along with depletion of glutathione, the most abundant endogenous antioxidant. Therefore, boosting endogenous glutathione has been proposed as a therapeutic strategy to prevent muscle wasting.

Association between genetic polymorphisms of cadherin 23 and noise-induced hearing loss: a meta-analysis.

Background: NIHL is one of the most common occupational diseases induced by gene-environment interaction. The gene is a candidate gene related to NIHL susceptibility. However, the relationship between gene and NIHL is still inconclusive.

Neutralization of GDF15 Prevents Anorexia and Weight Loss in the Monocrotaline-Induced Cardiac Cachexia Rat Model.

Growth and differentiation factor 15 (GDF15) is a cytokine reported to cause anorexia and weight loss in animal models. Neutralization of GDF15 was efficacious in mitigating cachexia and improving survival in cachectic tumor models. Interestingly, elevated circulating GDF15 was reported in patients with pulmonary arterial hypertension and heart failure, but it is unclear whether GDF15 contributes to cachexia in these disease conditions.

Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation.

Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose.

Fc-GDF15 glyco-engineering and receptor binding affinity optimization for body weight regulation.

GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, GDF15 has attracted attention as a potential therapeutic for the treatment of obesity and its associated metabolic diseases. However, the pharmacokinetic and physicochemical properties of GDF15 present several challenges for its development as a therapeutic, including a short half-life, high aggregation propensity, and protease susceptibility in serum.

Effects of Long-Term Nitrogen Fertilization on the Formation of Metabolites Related to Tea Quality in Subtropical China.

As a main agronomic intervention in tea cultivation, nitrogen (N) application is useful to improve tea yield and quality. However, the effects of N application on the formation of tea quality-related metabolites have not been fully studied, especially in long-term field trials. In this study, a 10-year field experiment was conducted to investigate the effect of long-term N application treatments on tea quality-related metabolites, their precursors, and related gene expression.

Identification of expression as a potential prognostic biomarker guiding treatment choice in acute myeloid leukemia.

Changes in lipid metabolism affect numerous cellular processes that are relevant to cancer biology, including cell proliferation, death, differentiation and motility. In the phosphatidylcholine biosynthesis pathway, the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine is catalyzed by cytosolic enzymes of the LPC acyltransferase (LPCAT) family. A number of studies have demonstrated that overexpression is a frequent event in diverse human cancer types, and that it is associated with unfavorable pathological characteristics and patient survival.

GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates.

Platinum-based cancer therapy is restricted by dose-limiting side effects and is associated with elevation of growth differentiation factor 15 (GDF-15). But whether this elevation contributes to such side effects has been unclear. Here, we explored the effects of GDF-15 blockade on platinum-based chemotherapy-induced emesis, anorexia, and weight loss in mice and/or nonhuman primate models.

Characterization of cachexia in the human fibrosarcoma HT-1080 mouse tumour model.

Background: Cancer cachexia is a complex metabolic disease with unmet medical need. Although many rodent models are available, none are identical to the human disease. Therefore, the development of new preclinical models that simulate some of the physiological, biochemical, and clinical characteristics of the human disease is valuable.

GDF15 Induces an Aversive Visceral Malaise State that Drives Anorexia and Weight Loss.

The anorectic and weight-suppressive effects of growth differentiation factor-15 (GDF15) are attracting considerable attention for treating obesity. Current experiments in rats investigate whether GDF15 induces an aversive visceral malaise-based state that mediates its acute anorectic effect and, through aversion conditioning, exerts longer-term anorexia. Visceral malaise, conditioned affective food responses (taste reactivity), gastric emptying (GE), food intake, and body weight are evaluated after acute and chronic systemic dosing of GDF15 or long-acting Fc-GDF15.

[Arthroscopic Twin Tail TightRope combined with distal joint capsule repair technique for acute acromioclavicular dislocation].

Objective: To investigate arthroscopic treatment for acute acromioclavicular dislocation by using Twin Tail TightRope combined with distal joint capsular repair.

Methods: The clinical data of 40 patients with acromioclavicular dislocation treated between February 2016 and December 2017 were retrospectively analyzed. The patients were divided into arthroscopic group (20 cases, using arthroscopic Twin Tail TightRope combined with distal joint capsular repair for anatomical repair of stable structure of acromioclavicular joint) and control group (20 cases, treated with clavicular hook plate internal fixation) according to different surgical methods.

[Arthroscopic treatment of irreducible hip posterior dislocation caused by acetabular labrum bony Bankart lesions].

Objective: To investigate the effectiveness of arthroscopic treatment for irreducible hip posterior dislocation caused by acetabular labrum bony Bankart lesions.

Methods: Between February 2008 and August 2016, 11 patients with irreducible hip posterior dislocation caused by acetabular labrum bony Bankart lesions, were treated with arthroscopic reduction and fixation of bony Bankart lesions. There were 7 males and 4 females, with an average age of 23.

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression.

Structural and functional characterization of MBS301, an afucosylated bispecific anti-HER2 antibody.

MBS301, a glyco-engineered bispecific anti-human epidermal growth factor receptor 2 (HER2) antibody with a typical IgG1 monoclonal antibody structure, was developed through dual-cell expression and in vitro assembling process. MBS301 consists of two half antibodies engineered from trastuzumab and pertuzumab, respectively. Integrity and purity profiles of MB301 indicated that the heterodimerization of the two half antibodies was successful.

Sucrose Nonfermenting-Related Kinase Regulates Both Adipose Inflammation and Energy Homeostasis in Mice and Humans.

Sucrose nonfermenting-related kinase (SNRK) is a member of the AMPK-related kinase family, and its physiological role in adipose energy homeostasis and inflammation remains unknown. We previously reported that SNRK is ubiquitously and abundantly expressed in both white adipose tissue (WAT) and brown adipose tissue (BAT), but SNRK expression diminishes in adipose tissue in obesity. In this study we report novel experimental findings from both animal models and human genetics.

The outcomes of the modified Fulkerson osteotomy procedure to treat habitual patellar dislocation associated with high-grade trochlear dysplasia.

Background: Habitual patellar dislocation is not common in clinical practice, but it has a deep impact on the patient's lifestyle and movement. There has been no large case-control study on habitual patellar dislocation, and the management of it is still controversial. The aim of this study was to observe the efficacy of the modified Fulkerson procedure on patients with habitual patellar dislocation with high-grade trochlear dysplasia without trochleoplasty and to evaluate the results of this procedure.

[Arthroscopic treatment of both anterior and posterior cruciate ligament tibial insertion avulsion fractures with suture and absorbable screw double fixation].

Objective: ?To evaluate the effectiveness of arthroscopic suture and absorbable screw double fixation for both anterior and posterior cruciate ligament avulsion fractures of tibial insertions.

Methods: ?Between June 2006 and September 2013, 8 patients with anterior and posterior cruciate ligament avulsion fractures of the tibial eminence underwent arthroscopic treatment with suture and absorbable screw double fixation. There were 5 males and 3 females, with a mean age of 28.