Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment

Sound Effects on Physiological State and Behavior of Drivers in a Highway Tunnel

Driving behavior in a highway tunnel could be affected by external environmental factors like light, traffic flow, and acoustic environments, significantly when these factors suddenly change at the moment before and after entering a tunnel. It will cause tremendous physiological pressure on drivers because of the reduction of information and the narrow environment. The risks in driving behavior will increase, making drivers more vulnerable than driving on the regular highways. This research focuses on the usually neglected acoustic environment and its effect on drivers' physiological state and driving behavior. Based on the SIMLAB driving simulation platform of a highway tunnel, 45 drivers participated in the experiment. Five different sound scenarios were tested: original highway tunnel sound and a mix of it with four other sounds (slow music, fast music, voice prompt, and siren, respectively). The subjects' physiological state and driving behavior data were collected through heart rate variability (HRV) and electroencephalography (EEG). Also, vehicle operational data, including vehicle speed, steering wheel angle, brake pedal depth, and accelerator pedal depth, were collected. The results indicated that different sound scenarios in the highway tunnel showed significant differences in vehicle speed (p = 0.000, η2 = 0.167) and steering wheel angle (p = 0.007, η2 = 0.126). At the same time, they had no significant difference in HRV and EEG indicators. According to the results, slow music was the best kind of sound related to driving comfort, while the siren sound produced the strongest driver reaction in terms of mental alertness and stress level. The voice-prompt sound most likely caused driver fatigue and overload, but it was the most effective sound affecting safety. The subjective opinion of the drivers indicated that the best sound scenario for the overall experience was slow music (63%), followed by fast music (21%), original highway tunnel sound environment (13%), and voice-prompt sound (3%). The findings of this study will be valuable in improving acoustic environment quality and driving safety in highway tunnels

Helicobacter Pylori Infection Correlates with Lower Prevalence and Subsequent Incidence of Crohn’s Disease

According to some researchs, Crohn’s disease (CD) and Ulcerative colitis (UC), two chronic inflammatory bowel illnesses, may be protected against Helicobacter pylori infection. Many case–control studies have revealed that individuals with CD and UC had lower H. pylori prevalence than healthy controls. However, whether or not H. pylori plays a protective role in the development of Crohn’s disease is debatable. CD was more common in H. pylori-negative individuals than in H. pylori-positive patients. After eradication of H. pylori, the CD was more common in the H. pylori-negative group than in the H. pylori-positive group over the previous research follow-up period. Although it has been strongly indicated in previous studies that H. pylori infection plays a significant role and triggers autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases, the role of H. pylori in inflammatory bowel disease, including Crohn’s disease, is unclear

Oncogenic PIK3CA Mutations Reprogram Glutamine Metabolism in Colorectal Cancer

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations

Oncogenic PIK3CA Mutations Reprogram Glutamine Metabolism in Colorectal Cancer

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to alpha-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110 alpha upregulates GPT2 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Targeting glutamine metabolism in PIK3CA mutant colorectal cancers

We recently reported that PIK3CA mutant colorectal cancers (CRCs) are addicted to glutamine through up-regulation of glutamate pyruvate transaminase 2 (GPT2). A GPT2 inhibitor suppresses in vivo growth of PIK3CA mutant, but not wild-type, CRCs. This study indicates that targeting glutamine may be an effective approach to treat CRCs with PIK3CA mutations

OsJAZ13 Negatively Regulates Jasmonate Signaling and Activates Hypersensitive Cell Death Response in Rice

Jasmonate ZIM-domain (JAZ) proteins belong to the subgroup of TIFY family and act as key regulators of jasmonate (JA) responses in plants. To date, only a few JAZ proteins have been characterized in rice. Here, we report the identification and function of rice OsJAZ13 gene. The gene encodes three different splice variants: OsJAZ13a, OsJAZ13b, and OsJAZ13c. The expression of OsJAZ13 was mainly activated in vegetative tissues and transiently responded to JA and ethylene. Subcellular localization analysis indicated OsJAZ13a is a nuclear protein. Yeast two-hybrid assays revealed OsJAZ13a directly interacts with OsMYC2, and also with OsCOI1, in a COR-dependent manner. Furthermore, OsJAZ13a recruited a general co-repressor OsTPL via an adaptor protein OsNINJA. Remarkably, overexpression of OsJAZ13a resulted in the attenuation of root by methyl JA. Furthermore, OsJAZ13a-overexpressing plants developed lesion mimics in the sheath after approximately 30–45 days of growth. Tillers with necrosis died a few days later. Gene-expression analysis suggested the role of OsJAZ13 in modulating the expression of JA/ethylene response-related genes to regulate growth and activate hypersensitive cell death. Taken together, these observations describe a novel regulatory mechanism in rice and provide the basis for elucidating the function of OsJAZ13 in signal transduction and cell death in plants

Relationship among post-traumatic growth, spiritual well-being, and perceived social support in Chinese women with gynecological cancer

Abstract This study aimed to examine the correlation between post-traumatic growth (PTG), spiritual well-being (SWB), perceived social support (PSS), and demographic and clinical factors in Chinese gynecological cancer patients. Through convenience sampling, we conducted a cross-sectional study of 771 adult patients with gynecological cancer. The European Organization for Research and Treatment for Cancer Quality of Life Questionnaire-Spiritual Well-being 32 (EORTC QLQ-SWB32), Post-traumatic Growth Inventory (PTGI), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to measure SWB, PTG, and PSS. A Multiple Linear Regression Model was used to determine the possible factors contributing to PTG. The subscale with the highest centesimal score in the PTGI was the Appreciation of Life Scale, and the lowest was New Possibility. Gynecologic cancer patients with younger ages (B =  − 0.313, P = 0.002), perceived more family support (B = 1.289, P < 0.001), had more existential (B = 0.865, P = 0.010), and had religious belief (B = 5.760, P = 0.034) may have more PTG. Spiritual well-being, perceived social support, younger age, and religious beliefs are associated with post-traumatic growth in gynecological cancer patients. Healthcare staff could provide more professional support to younger patients with religious beliefs. Promoting social support and spiritual well-being could potentially serve as effective interventions for boosting PTG among gynecological cancer

The great potential of flavonoids as candidate drugs for NAFLD

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of approximately 25 % and is associated with high morbidity and high mortality. NAFLD is a leading cause of cirrhosis and hepatocellular carcinoma. Its pathophysiology is complex and still poorly understood, and there are no drugs used in the clinic to specifically treat NAFLD. Its pathogenesis involves the accumulation of excess lipids in the liver, leading to lipid metabolism disorders and inflammation. Phytochemicals with the potential to prevent or treat excess lipid accumulation have recently received increasing attention, as they are potentially more suitable for long-term use than are traditional therapeutic compounds. In this review, we summarize the classification, biochemical properties, and biological functions of flavonoids and how they are used in the treatment of NAFLD. Highlighting the roles and pharmacological uses of these compounds will be of importance for enhancing the prevention and treatment of NAFLD