Genomic and transcriptomic profiling of inflammatory breast cancer reveals distinct molecular characteristics to non-inflammatory breast cancers.

PURPOSE: Inflammatory breast cancer (IBC), a rare and highly aggressive form of breast cancer, accounts for 10% of breast cancer-related deaths. Previous omics studies of IBC have focused solely on one of genomics or transcriptomics and did not discover common differences that could distinguish IBC from non-IBC. METHODS: Seventeen IBC patients and five non-IBC patients as well as additional thirty-three Asian breast cancer samples from TCGA-BRCA were included for the study. We performed whole-exon sequencing (WES) to investigate different somatic genomic alterations, copy number variants, and large structural variants between IBC and non-IBC. Bulk RNA sequencing (RNA-seq) was performed to examine the differentially expressed genes, pathway enrichment, and gene fusions. WES and RNA-seq data were further investigated in combination to discover genes that were dysregulated in both genomics and transcriptomics. RESULTS: Copy number variation analysis identified 10 cytobands that showed higher frequency in IBC. Structural variation analysis showed more frequent deletions in IBC. Pathway enrichment and immune infiltration analysis indicated increased immune activation in IBC samples. Gene fusions including CTSC-RAB38 were found to be more common in IBC. We demonstrated more commonly dysregulated RAS pathway in IBC according to both WES and RNA-seq. Inhibitors targeting RAS signaling and its downstream pathways were predicted to possess promising effects in IBC treatment. CONCLUSION: We discovered differences unique in Asian women that could potentially explain IBC etiology and presented RAS signaling pathway as a potential therapeutic target in IBC treatment.

Postoperative fever and clinical outcomes after endoscopic surgery for spontaneous intracerebral hemorrhage: a retrospective database study.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is a severe stroke with high mortality and disability rates. Endoscopic surgery is an increasingly widely used minimally invasive method for the treatment of SICH. However, the impact of fever on patient outcomes remains unclear. METHODS: We retrospectively included patients aged 18 years or older with supratentorial SICH confirmed by CT, who underwent endoscopic hematoma evacuation within 48 h of symptom onset. The primary outcome was the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes included hospital and neurosurgical intensive care unit (NSICU) stays, and perioperative complications. We analyzed the association between postoperative fever (highest temperature within 24 h after surgery) and these outcomes using multivariate analysis, generalized additive models, and segmented regression analysis. RESULTS: Of the 56 patients, 38 had favorable outcomes (mRS ≤ 3) and 18 had unfavorable outcomes (mRS > 3) at 3 months. A threshold effect at 38.2 °C was observed between postoperative body temperature and clinical outcomes. The mean age was 56 years (SD = 9) for the > 38.2 °C group and 58 years (SD = 8) for the ≤ 38.2 °C group, with a similar proportion of male patients (63% vs. 69%, P = 0.635). Patients with postoperative fever had larger hematoma volumes (65 vs. 56 mL; P = 0.008). Other characteristics were similar between the groups. Postoperative fever (> 38.2 °C) was independently associated with a 4.99-fold increased risk of unfavorable outcomes (95% CI = [1.13 to 25.90]; P = 0.040), which remained significant after excluding patients with postoperative complications (adjusted RR = 16.03, 95% CI = [1.69 to 417.24]; P = 0.033). The association was consistent across subgroups with different Glasgow Coma Scale scores, hematoma volumes, and intraventricular extension. Postoperative fever was also associated with longer NSICU stays (3.1 vs. 2.3 days; P = 0.023), longer hospital stays (17.2 vs. 13.6 days; P = 0.010), more residual hematoma, and greater edema volume. Different antipyretic therapies did not affect outcomes. CONCLUSIONS: This study identifies a temperature threshold (38.2 °C) associated with poor outcomes in SICH patients undergoing endoscopic surgery. Further research is needed to mitigate postoperative fever and improve patient outcomes.

The Efficacy of Low-Kilovoltage X-Rays Intraoperative Radiation as Boost for Breast Cancer: A Systematic Review and Meta-Analysis.

Background: Intraoperative radiotherapy (IORT) is a novel promising technology that may replace external beam radiation therapy (EBRT) as boost for patients receiving breast-conserving surgery. To better evaluate the efficacy of IORT using low-kilovoltage (low-kV) X-rays as boost, we presented this meta-analysis according to the PRISMA checklist. Methods: Studies reported survival outcomes of intraoperative radiation using low-kilovoltage X-rays system (Intrabeam®, Carl Zeiss Meditec, Dublin, CA, USA) as boost were identified through electronic bibliographic database: PUBMED. The meta-analysis module in Stata (16.0) is used to pool the studies. A Poisson regression model is used to predict a 5-year local recurrence rate. Results: Twelve studies including 3006 cases were included in the final analysis, with a median follow-up of 55 months weighted by sample size. The pooled local recurrence rate is 0.39% per person-year (95% CI: 0.15%-0.71%), with a low degree of heterogeneity (I2 = 0%). The predicted 5-year local recurrence rate was 3.45%. No difference in pooled local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies (0.41% per person-year vs. 0.58% per person-year, P = 0.580). Conclusions: This study shows that low-kV IORT is an effective method as boost in breast cancer patients, with a low pooled local recurrence rate and low predicted 5-year local recurrence rate. Besides, no difference in the local recurrence rate was found between non-neoadjuvant patients studies and neoadjuvant patients studies. Low-kV IORT boost may be a promising alternative to EBRT boost in the future, which is being tested in the ongoing TARGIT-B trial.

A novel CACNA1S gene variant in a child with hypokalemic periodic paralysis: a case report and literature review.

BACKGROUND: The CACNA1S gene encodes the alpha 1 S-subunit of the voltage-gated calcium channel, which is primarily expressed in the skeletal muscle cells. Pathogenic variants of CACNA1S can cause hypokalemic periodic paralysis (HypoPP), malignant hyperthermia susceptibility, and congenital myopathy. We aimed to study the clinical and molecular features of a male child with a CACNA1S variant and depict the molecular sub-regional characteristics of different phenotypes associated with CACNA1S variants. CASE PRESENTATION: We presented a case of HypoPP with recurrent muscle weakness and hypokalemia. Genetic analyses of the family members revealed that the proband had a novel c.497 C > A (p.Ala166Asp) variant of CACNA1S, which was inherited from his father. The diagnosis of HypoPP was established in the proband as he met the consensus diagnostic criteria. The patient and his parents were informed to avoid the classical triggers of HypoPP. The attacks of the patient are prevented by lifestyle changes and nutritional counseling. We also showed the molecular sub-regional location of the variants of CACNA1S which was associated with different phenotypes. CONCLUSIONS: Our results identified a new variant of CACNA1S and expanded the spectrum of variants associated with HypoPP. Early genetic diagnosis can help avoid diagnostic delays, perform genetic counseling, provide proper treatment, and reduce morbidity and mortality.

A System of Emotion Recognition and Judgment and Its Application in Adaptive Interactive Game.

A system of emotion recognition and judgment (SERJ) based on a set of optimal signal features is established, and an emotion adaptive interactive game (EAIG) is designed. The change in a player's emotion can be detected with the SERJ during the process of playing the game. A total of 10 subjects were selected to test the EAIG and SERJ. The results show that the SERJ and designed EAIG are effective. The game adapted itself by judging the corresponding special events triggered by a player's emotion and, as a result, enhanced the player's game experience. It was found that, in the process of playing the game, a player's perception of the change in emotion was different, and the test experience of a player had an effect on the test results. A SERJ that is based on a set of optimal signal features is better than a SERJ that is based on the conventional machine learning-based method.

The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis.

Histone deacetylase inhibitor (HDACi) is a drug mainly used to treat hematological tumors and breast cancer, but its inhibitory effect on breast cancer falls short of expectations. Grape seed proanthocyanidin extract (GSPE) with abundant proanthocyanidins (PAs) has been explored for its inhibition of HDAC activity in vitro and in vivo. To enhance HDACi's effectiveness, we investigated the potential of PA to synergistically enhance HDACi chidamide (Chi), and determined the underlying mechanism. We evaluated the half-inhibitory concentration (IC50) of PA and Chi using the cell counting kit 8 (CCK8), and analyzed drugs' synergistic effect with fixed-ratio combination using the software Compusyn. Breast cancer cell's phenotypes, including short-term and long-term proliferation, migration, invasion, apoptosis, and reactive oxygen species (ROS) levels, were assessed via CCK8, clone-formation assay, wound-healing test, Transwell Matrigel invasion assay, and flow-cytometry. Protein-protein interaction analysis (PPI) and KEGG pathway analysis were used to determine the underlying mechanism of synergy. PA + Chi synergistically inhibited cell growth in T47D and MDA-MB-231 breast cancer cell lines. Short-term and long-term proliferation were significantly inhibited, while cell apoptosis was promoted. Ten signaling pathways were identified to account for the synergistic effect after RNA sequencing. Their synergism may be closely related to the steroid biosynthesis and extracellular matrix (ECM) receptor interaction pathways. PA + Chi can synergistically inhibit breast cancer cell growth and proliferation, and promote apoptosis. These effects may be related to steroid biosynthesis or the ECM receptor pathway.

Effects and mechanisms of resveratrol for prevention and management of cancers: An updated review.

Cancer is a severe public health problem. Resveratrol is a famous natural compound that has various bioactivities, such as antioxidant, anti-inflammatory, antidiabetic and antiaging activities. Especially, resveratrol could prevent and treat various cancers, such as oral, thyroid, breast, lung, liver, pancreatic, gastric, colorectal, bladder, prostate and ovarian cancers. The underlying mechanisms have been widely studied, such as inhibiting cell proliferation, suppressing metastasis, inducing apoptosis, stimulating autophagy, modulating immune system, attenuating inflammation, regulating gut microbiota and enhancing effects of other anticancer drugs. In this review, we summarize effects and mechanisms of resveratrol on different cancers. This paper is helpful to develop resveratrol, crude extract containing resveratrol, or foods containing resveratrol into functional food, dietary supplements or auxiliary agents for prevention and management of cancers.

Association between exposure to air pollutants and the risk of hospitalization for pulmonary embolism in Beijing, China: A case-crossover design using a distributed lag nonlinear model.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening condition. Few studies have evaluated the relationship between air pollution and PE, and these results have been inconsistent. Therefore, our study aimed to investigate the association between air pollutant exposure and the risk of hospitalization due to PE. MATERIALS AND METHODS: Daily PE admissions, meteorological data, and ambient pollution data from January 1, 2015, to December 31, 2018, were collected in Beijing. A quasi-Poisson regression model combined with time-stratified case-crossover design and a distributed lag nonlinear model was used to determine the effect of air pollutant exposure on PE admission. To examine the stability of air pollutants' effects, multi-pollutant analyses were performed. Stratified analyses by age and sex were further conducted. RESULTS: There were 5060 PE admissions during the study period, with an estimated incidence of 6.5 per 100,000. PM2.5, PM10, SO2, O3 and CO exposures were significantly associated with elevated risk of PE hospitalization. The highest cumulative risks were observed at a lag of 0-28 days for PM2.5 (relative risk [RR] = 1.056, 95% confidence intervals [CI]: 1.015-1.098), PM10 (RR = 1.042, 95%CI: 1.010-1.075), and CO (RR = 1.466, 95%CI: 1.127-1.906), at a lag of 0-27 days for SO2 (RR = 1.674, 95%CI: 1.200-2.335), and at a lag of 0-4 days for O3 (RR = 1.019, 95%CI: 1.001-1.038). All associations mentioned above except O3 remained significant in multi-pollutant models. Stratified analyses showed that women and those aged ≥65 years people were more sensitive to PM10 and CO exposure than men and those aged <65 years. The effect of PM2.5 exposure was statistically significant in all subgroups. CONCLUSIONS: Exposure to PM2.5, PM10, SO2, and CO showed a positive association with PE hospitalization. High-risk PE groups should take special precautions on days with poor air quality.

Prognosis assessment model based on low serum calcium in patients with acute pulmonary thromboembolism.

BACKGROUND AND OBJECTIVE: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. METHODS: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. RESULTS: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid- and long-term mortalities (p <0.05). By including hypocalcaemia, the new 30-day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well-performing predictive validity was also verified on a constructed external validation cohort. CONCLUSION: Hypocalcaemia is independently associated with mid- and long-term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE.

A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ systems. Moxifloxacin has rarely been reported to be a drug that is associated with DRESS syndrome. Lungs are less frequently involved in DRESS syndrome, but their involvements may herald more serious clinical processes. We present a rare typical case of moxifloxacin-induced DRESS syndrome with lungs involved. Valuable clinical data such as changes in the pulmonary imaging and pulmonary function tests was recorded. This case is important for the differential diagnosis of DRESS syndrome with lungs involved by providing clinical manifestations, CT imaging, pulmonary function tests, and biopsy pathological characteristics. The changes in pulmonary imaging and pulmonary function tests may help us understand the mechanism of DRESS syndrome further. CASE PRESENTATION: We report a case of a 47-year-old woman who was treated with oral moxifloxacin for community-acquired pneumonia. The patient subsequently developed a cough, fever, liver injury, skin rash, hematologic abnormalities, and shortness of breath (SOB) followed by pharyngeal herpes and peripheral neuritis. These symptoms, clinical lab index, and CT scan of the lungs improved after the withdrawal of moxifloxacin. The probability of moxifloxacin-induced DRESS syndrome was rated as "Definite", with 7 scores graded by RegiSCAR. A literature search was also performed with "fluoroquinolones," "moxifloxacin," "ciprofloxacin," "levofloxacin," "delafloxacin," and "DRESS" or "drug-induced hypersensitivity syndrome (DIHS)" as the keywords that were put into PubMed. The overall pulmonary involvement was approximately 9.1% (1/11). It is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. We summarized detailed clinical data, including pulmonary imaging and pulmonary function changes. CONCLUSION: This is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. Prompt recognition and correct diagnosis can promote appropriate treatment and accelerate recovery. This case is important for us as a reference in the differential diagnosis of DRESS syndrome and helps us further understand the mechanism of DRESS syndrome.

Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis.

Mirabegron (Myrbetriq) is a ß3-adrenoreceptor agonist approved for treating overactive bladder syndrome in human patients. This drug can activate brown adipose tissue (BAT) in adult humans and rodents through the ß3-adrenoreceptor-mediated sympathetic activation. However, the effect of the mirabegron, approved by the US Food and Drug Administration, on atherosclerosis-related cardiovascular disease is unknown. Here, we show that the clinical dose of mirabegron-induced BAT activation and browning of white adipose tissue (WAT) exacerbate atherosclerotic plaque development. In apolipoprotein E-/- (ApoE-/-) and low-density lipoprotein (LDL) receptor-/- (Ldlr-/-) mice, oral administration of clinically relevant doses of mirabegron markedly accelerates atherosclerotic plaque growth and instability by a mechanism of increasing plasma levels of both LDL-cholesterol and very LDL-cholesterol remnants. Stimulation of atherosclerotic plaque development by mirabegron is dependent on thermogenesis-triggered lipolysis. Genetic deletion of the critical thermogenesis-dependent protein, uncoupling protein 1, completely abrogates the mirabegron-induced atherosclerosis. Together, our findings suggest that mirabegron may trigger cardiovascular and cerebrovascular diseases in patients who suffer from atherosclerosis.

Interactive Application of Data Glove Based on Emotion Recognition and Judgment System.

In this paper, the interactive application of data gloves based on emotion recognition and judgment system is investigated. A system of emotion recognition and judgment is established based on the set of optimal features of physiological signals, and then a data glove with multi-channel data transmission based on the recognition of hand posture and emotion is constructed. Finally, the system of virtual hand control and a manipulator driven by emotion is built. Five subjects were selected for the test of the above systems. The test results show that the virtual hand and manipulator can be simultaneously controlled by the data glove. In the case that the subjects do not make any hand gesture change, the system can directly control the gesture of the virtual hand by reading the physiological signal of the subject, at which point the gesture control and emotion control can be carried out at the same time. In the test of the manipulator driven by emotion, only the results driven by two emotional trends achieve the desired purpose.

Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review.

Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.

Breast lesions excised via vacuum-assisted system: could we get any clues for B3 lesions before excision biopsy?

BACKGROUND: The purpose of this study was to determine the validity of the ultrasound features as well as patient characteristics assigned to B3 (uncertain malignant potential) breast lesions before vacuum-assisted excision biopsy (VAEB). METHODS: This study population consisted of 2245 women with breast-nodular abnormalities, which were conducted ultrasound-guided VAEB (US-VAEB). Patient's clinical and anamnestic data and lesion-related ultrasonic feature variables of B3 captured before US-VAEB were compared with those of benign or malignant cases, using histopathological results as a benchmark. RESULTS: The proportions of benign, B3 and malignant breast lesions diagnosed post-US-VAEB were 88.5, 8.2 and 3.4% respectively. B3 high frequent occurred in BI-RADS-US grade 3 (7.7%), grade 4a (11.0%) and grade 4b (9.1%). The overall malignancy underestimation rate of B3 was 4.4% (8/183). Malignant lesions were found mostly in the range of BI-RADS grade 4b (27.3%), grade 4c (33.3%) and grade 5 (100%). Multivariate binary logistic regression analyses (B3 vs benign) showed that non-menopausal patients (95% CI 1.628-8.616, P = 0.002), single (95% CI 1.370-2.650, P = 0.000) or vascularity (95% CI 1.745-4.150, P = 0.000) nodules in ultrasonic features were significant risk factors for B3 occurrences. In addition, patients elder than 50 years (95% CI 3.178-19.816, P = 0.000), unclear margin (95% CI 3.571-14.119, P = 0.000) or suspicious calcification (95% CI 4.010-30.733, P = 0.000) lesions were significantly associated with higher risks of malignant potentials for B3 cases (malignant vs B3). CONCLUSION: The results of this study indicate that ultrasound findings and patients' characteristics might provide valuable information for distinguishing B3 lesions from benign breast abnormalities before VAEB, and help to reduce malignancy underestimation of B3.

Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer.

BACKGROUND: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer. METHODS: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions. RESULTS: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer. CONCLUSION: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.

Developmental Regression and Epilepsy of Infancy with Migrating Focal Seizures Caused by TBCD Mutation: A Case Report and Review of the Literature.

Microtubule dynamics plays a crucial role in neuronal development and function. Variants in the tubulin cofactor D (TBCD) gene, which encodes one of the five co-chaperones required for assembly and disassembly of α/ß-tubulin heterodimers, may lead to neurodevelopmental disorders. We aimed to study the clinical, electroencephalographic, and imaging features of a male patient with TBCD variants, and to provide a detailed review of the previously reported cases of TBCD-related neurological disorders. The patient presented with early-onset developmental regression, secondary microcephaly, epilepsy of infancy with migrating focal seizures, hypotonia, and brain atrophy with thin corpus callosum on brain magnetic resonance imaging. Genetic analyses of the family members revealed a compound heterozygous variant of c.230A > G (p.H77R) in the proband and deletion of exons 28 to 39 of TBCD, which has not been previously reported and was inherited from his carrier parents. Epilepsy of the patient was refractory to numerous antiepileptic drugs. The review of 33 previously reported patients revealed that the age at the onset was very early, and all the patients had presentations during the first year of life. This case report provides insight regarding the clinical features and genetic etiology of TBCD-related tubulinopathy. Identification of phenotypes and genotypes in patients may help in early diagnosis and appropriate genetic counseling.

Proanthocyanidins Should Be a Candidate in the Treatment of Cancer, Cardiovascular Diseases and Lipid Metabolic Disorder.

The conventional view of using medicines as routine treatment of an intractable disease is being challenged in the face of extensive and growing evidence that flavonoids in foods, especially proanthocyanidins (PAs), can participate in tackling fatal diseases like cancer, cardiovascular and lipid metabolic diseases, both as a precautionary measure or as a dietary treatment. Although medical treatment with medicines will remain necessary in some cases, at least in the short term, PAs' function as antioxidant, anti-inflammatory drugs, signal pathway regulators remain critical in many diseases. This review article demonstrates the physical and biological properties of PAs, summarizes the health benefits of PAs found by researchers previously, and shows the possibility and importance of being a dietary treatment substance.

miR-96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high-fat-diet-induced dyslipidemia in mice.

We aimed to investigate the possible signaling pathways underlying the regulation of grape seed proanthocyanidins extracts (GSPE) on lipid metabolism. One hundred male C57BL/6 mice were divided into four groups: control group (normal diet), GSPE group (normal diet + GSPE), high-fat diet group (HFD), and high-fat diet plus GSPE (200 mg/kg/day) group (HFD + GSPE). Mice received the diets for 180 days. Body weight and serum lipid levels were measured. Autophagic flux characteristics, such as accumulation of lipids, mitochondria, and autophagosomes in the liver, were detected using transmission electron microscopy. Expression profile of microRNAs (miRNAs) in the liver was determined using RNA microarray and quantitative real time polymerase chain reaction (qRt-PCR). GSPE significantly decreased the weight gain, serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol but increased high-density lipoprotein cholesterol in the HFD mice. Autophagic flux was significantly increased by HFD but decreased by GSPE treatment. GSPE significantly attenuated HFD-induced miR-96 upregulation, which in turn reduced the expressions of miR-96 downstream molecules, FOXO1, mTOR, p-mTOR, and LC3A/B. These results suggested that the miR-96 is involved in the protective effect of GSPE against HFD-induced dyslipidemia. Possible mechanisms might be through mTOR and FOXO1, which facilitate autophagic flux for clearance of lipid accumulation.

Pesticide exposure and risk of Parkinson's disease: Dose-response meta-analysis of observational studies.

The cause of late onset Parkinson's disease (PD) remains unknown. Evidence suggested that lifelong exposure to pesticides might contribute to the development of neurodegenerative diseases, but the results were controversial. Relevant studies were identified by searching PubMed and Web of Science through September 2017. We included cohort and case-control studies reporting relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) of three or more categories of pesticide exposure and PD. Ten articles with 13 reports (3 for cumulative exposure, 10 for duration exposure) were included. A nonlinearity association was seen between duration exposure and PD risk (P = 0.01 for nonlinearity). The summary ORs of developing PD for 5 and 10 years of duration exposure were 1.05 (95% CI: 1.02-1.09) and 1.11 (95% CI: 1.05-1.18), respectively. Sensitivity analyses with different effect models yielded similar results, and omission of any single study did not change the results. The 5 and 10 years of duration pesticide exposure were associated with a 5% and 11% augment in the risk of PD. Further high-quality cohort studies were required to validate a causal relationship.

Identification of key candidate genes, pathways and related prognostic values in ER-negative/HER2-negative breast cancer by bioinformatics analysis.

PURPOSE: Breast cancer possesses different molecular expressions and biological behaviors. The purpose of this study was to identify the key genes, pathways, and related prognostic values in estrogen receptor (ER)-negative/human epidermal growth factor 2 (HER2)-negative breast cancer by bioinformatics analysis. METHODS: The mRNA expression profiles of GSE20194 and GSE23988 were obtained from the Gene Expression Omnibus (GEO) database. Differently expressed genes (DEGs) were analyzed by GEO2R. A functional and pathway enrichment analysis of DEGs was conducted using DAVID. A protein-protein interaction (PPI) network was constructed using STRING and a module analysis of the PPI network was conducted using Cytoscape software. Survival analysis of hub genes was analyzed using the Kaplan-Meier plotter online tool. RESULTS: 108 ER-negative/HER2-negative and 172 ER-positive/HER2-negative breast cancer samples were collected from the datasets GSE20194 and GSE23988. A total of 355 DEGs were identified in the ER-negative/HER2-negative samples, including 140 up-regulated and 215 down-regulated genes. The PPI network of DEGs consisted of 265 nodes and 648 edges. A significant module (12 nodes and 56 edges) was acquired from the PPI network of DEGs. Geneontology (GO) and pathway enrichment analysis demonstrated that this module was mainly related with transcription, cell proliferation, binding, and pathways in the PI3K-Akt signaling pathway. The high expression of CCNE1, KRT16, and MYBL2 was associated with worse relapse-free survival (RFS) and overall survival (OS) in ER-negative/HER2-negative breast cancer. CONCLUSIONS: An integrated bioinformatics analysis was utilized to discover key candidate genes and pathways in ER-negative/HER2-negative breast cancer. This can improve the understanding of molecular mechanisms and provide potential candidate genes for diagnosis, prognosis, and individualized therapy.